{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMCL1 is a pivotal anti‐apoptotic BCL2 family member that safeguards cell survival by directly sequestering key pro‐apoptotic effectors such as Bak and BH3‐only proteins. In healthy cells, MCL1 forms complexes with proteins like Bak to restrain mitochondrial outer membrane permeabilization and prevent the cascade leading to cytochrome c release and caspase activation. Moreover, in several contexts—from p53‐mediated apoptosis to death receptor–induced signaling—regulated disassembly or proteolytic processing of MCL1 is required to trigger the apoptotic programme. These studies collectively highlight how MCL1 functions as a critical “gatekeeper” of apoptosis by controlling the activation status and localization of pro‐apoptotic molecules."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe stability and turnover of MCL1 are subject to tight post‐translational regulation that is central to its role as an apoptosis rheostat. Several studies have demonstrated that phosphorylation events—mediated by kinases such as glycogen synthase kinase‑3 (GSK‑3) and JNK—mark MCL1 for polyubiquitination by E3 ubiquitin ligases including Mule, beta‑TrCP, and FBW7. Additionally, deubiquitinases such as USP9X can counteract this process to stabilize MCL1, thus providing fine‐tuned control of its abundance. This dynamic regulation, involving both modifications that promote degradation and those that protect against it, underlies the diverse responses of cells to growth factor withdrawal, cytotoxic stress, and cell cycle cues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDeregulation of MCL1 expression is a hallmark of multiple malignancies and is closely linked to chemoresistance and disease relapse. Elevated MCL1 levels have been implicated in the survival of cancer stem cells in triple‐negative breast cancer, in the resistance of leukemias and lymphomas (including AML, CLL, and T‑ALL) to BH3 mimetics and conventional chemotherapeutics, and in the protection of tumor cells from mitochondrial-driven apoptosis triggered by oncogenic signals or microenvironmental cues. Oncogenic pathways—including those activated by B‑cell receptor engagement, FLT3‐ITD/STAT5 signaling, and epidermal growth factor—upregulate MCL1 either at the transcriptional or post‑transcriptional level (including via microRNA regulation), while impaired degradation of MCL1 underlies resistance to agents such as ABT‑737 and venetoclax. Collectively, these findings underscore MCL1’s central role in preserving malignant cell viability and highlight it as a promising therapeutic target in MCL1‑dependent cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Simon N Willis, Lin Chen, Grant Dewson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1304105"}], "href": "https://doi.org/10.1101/gad.1304105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15901672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15901672"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "J I-Ju Leu, Patrick Dumont, Michael Hafey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1123"}], "href": "https://doi.org/10.1038/ncb1123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15077116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15077116"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Changjiang Weng, Yuan Li, Dan Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M412819200"}], "href": "https://doi.org/10.1074/jbc.M412819200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15637055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15637055"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Magali Herrant, Arnaud Jacquel, Sandrine Marchetti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cleavage of Mcl-1 by caspases impaired its ability to counteract Bim-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1208069"}], "href": "https://doi.org/10.1038/sj.onc.1208069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15378010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15378010"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jie Han, Leslie A Goldstein, Brian R Gastman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interrelated roles for Mcl-1 and BIM in regulation of TRAIL-mediated mitochondrial apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M510349200"}], "href": "https://doi.org/10.1074/jbc.M510349200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16478725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16478725"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ulrich Maurer, Céline Charvet, Allan S Wagman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2006.02.009"}], "href": "https://doi.org/10.1016/j.molcel.2006.02.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16543145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16543145"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qing Zhong, Wenhua Gao, Fenghe Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2005.06.009"}], "href": "https://doi.org/10.1016/j.cell.2005.06.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15989957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15989957"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hiroyuki Inuzuka, Shavali Shaik, Ichiro Onoyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09732"}], "href": "https://doi.org/10.1038/nature09732"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21368833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21368833"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Martin Schwickart, Xiaodong Huang, Jennie R Lill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature08646"}], "href": "https://doi.org/10.1038/nature08646"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20023629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20023629"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Deepak Nijhawan, Min Fang, Elie Traer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1093903"}], "href": "https://doi.org/10.1101/gad.1093903"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12783855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12783855"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Qingqing Ding, Xianghuo He, Jung-Mao Hsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00620-06"}], "href": "https://doi.org/10.1128/MCB.00620-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17387146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17387146"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Bin Zhang, Ivana Gojo, Robert G Fenton "}, {"type": "b", "children": [{"type": "t", "text": "Myeloid cell factor-1 is a critical survival factor for multiple myeloma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood.v99.6.1885"}], "href": "https://doi.org/10.1182/blood.v99.6.1885"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11877256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11877256"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Stefan P Glaser, Erinna F Lee, Evelyn Trounson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.182980.111"}], "href": "https://doi.org/10.1101/gad.182980.111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22279045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22279045"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Seiji Inoshita, Kohsuke Takeda, Takiko Hatai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M207951200"}], "href": "https://doi.org/10.1074/jbc.M207951200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12223490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12223490"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Xiaojia Niu, Jianyun Zhao, Jun Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Binding of Released Bim to Mcl-1 is a Mechanism of Intrinsic Resistance to ABT-199 which can be Overcome by Combination with Daunorubicin or Cytarabine in AML Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-15-3057"}], "href": "https://doi.org/10.1158/1078-0432.CCR-15-3057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27103402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27103402"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Qingqing Ding, Longfei Huo, Jer-Yen Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of myeloid cell leukemia-1 through inhibiting Erk/Pin 1 pathway by sorafenib facilitates chemosensitization in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-0579"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-0579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18676833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18676833"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Kyung-Min Lee, Jennifer M Giltnane, Justin M Balko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2017.09.009"}], "href": "https://doi.org/10.1016/j.cmet.2017.09.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28978427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28978427"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Sophie Derenne, Brett Monia, Nicholas M Dean, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood.v100.1.194"}], "href": "https://doi.org/10.1182/blood.v100.1.194"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12070027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12070027"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Derek Yecies, Nicole E Carlson, Jing Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-07-233304"}], "href": "https://doi.org/10.1182/blood-2009-07-233304"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20197552"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20197552"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "G S Choudhary, S Al-Harbi, S Mazumder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2014.525"}], "href": "https://doi.org/10.1038/cddis.2014.525"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25590803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25590803"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Aleksandar Petlickovski, Luca Laurenti, Xiaoping Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-07-2669"}], "href": "https://doi.org/10.1182/blood-2004-07-2669"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15728130"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15728130"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Karl J Aichberger, Matthias Mayerhofer, Maria-Theresa Krauth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of mcl-1 as a BCR/ABL-dependent target in chronic myeloid leukemia (CML): evidence for cooperative antileukemic effects of imatinib and mcl-1 antisense oligonucleotides."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-02-0749"}], "href": "https://doi.org/10.1182/blood-2004-02-0749"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15626746"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15626746"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Laura M Sly, Suzanne M Hingley-Wilson, Neil E Reiner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Survival of Mycobacterium tuberculosis in host macrophages involves resistance to apoptosis dependent upon induction of antiapoptotic Bcl-2 family member Mcl-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.170.1.430"}], "href": "https://doi.org/10.4049/jimmunol.170.1.430"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12496428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12496428"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Goichi Yoshimoto, Toshihiro Miyamoto, Siamak Jabbarzadeh-Tabrizi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-12-196055"}], "href": "https://doi.org/10.1182/blood-2008-12-196055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19808698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19808698"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Irene M Pedersen, Shinichi Kitada, Lorenzo M Leoni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protection of CLL B cells by a follicular dendritic cell line is dependent on induction of Mcl-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12176902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12176902"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Wolfgang Sieghart, Doris Losert, Sabine Strommer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hepatol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jhep.2005.09.010"}], "href": "https://doi.org/10.1016/j.jhep.2005.09.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16289418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16289418"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Mathieu Derouet, Luke Thomas, Andrew Cross, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Granulocyte macrophage colony-stimulating factor signaling and proteasome inhibition delay neutrophil apoptosis by increasing the stability of Mcl-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M313875200"}], "href": "https://doi.org/10.1074/jbc.M313875200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15078892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15078892"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Chris Pepper, Thet Thet Lin, Guy Pratt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-05-157131"}], "href": "https://doi.org/10.1182/blood-2008-05-157131"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18599795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18599795"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Shogo Kobayashi, Nathan W Werneburg, Steven F Bronk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin-6 contributes to Mcl-1 up-regulation and TRAIL resistance via an Akt-signaling pathway in cholangiocarcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2005.03.010"}], "href": "https://doi.org/10.1053/j.gastro.2005.03.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15940637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15940637"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Lanxi Song, Domenico Coppola, Sandy Livingston, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mcl-1 regulates survival and sensitivity to diverse apoptotic stimuli in human non-small cell lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Ther (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cbt.4.3.1496"}], "href": "https://doi.org/10.4161/cbt.4.3.1496"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15753661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15753661"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Catherine L Day, Lin Chen, Sarah J Richardson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M411434200"}], "href": "https://doi.org/10.1074/jbc.M411434200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15550399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15550399"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Emilie Hollville, Richard G Carroll, Sean P Cullen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bcl-2 family proteins participate in mitochondrial quality control by regulating Parkin/PINK1-dependent mitophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2014.06.001"}], "href": "https://doi.org/10.1016/j.molcel.2014.06.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24999239"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24999239"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Patricia Pérez-Galán, Gaël Roué, Neus Villamor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-07-034173"}], "href": "https://doi.org/10.1182/blood-2006-07-034173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17227835"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17227835"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "S Gobessi, L Laurenti, P G Longo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of constitutive and BCR-induced Syk activation downregulates Mcl-1 and induces apoptosis in chronic lymphocytic leukemia B cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2008.346"}], "href": "https://doi.org/10.1038/leu.2008.346"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19092849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19092849"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Y Saito, H Suzuki, H Tsugawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.140"}], "href": "https://doi.org/10.1038/onc.2009.140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19503096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19503096"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Lei Jin, Wang Lai Hu, Chen Chen Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1019312108"}], "href": "https://doi.org/10.1073/pnas.1019312108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21896753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21896753"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Emily F Eckenrode, Jun Yang, Gopal V Velmurugan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Apoptosis protection by Mcl-1 and Bcl-2 modulation of inositol 1,4,5-trisphosphate receptor-dependent Ca2+ signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.096040"}], "href": "https://doi.org/10.1074/jbc.M109.096040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20189983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20189983"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Melissa Crawford, Kara Batte, Lianbo Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA 133B targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.07.143"}], "href": "https://doi.org/10.1016/j.bbrc.2009.07.143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19654003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19654003"}]}]}]}