{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSOCS7 is a multifunctional member of the suppressor of cytokine signaling family that regulates key intracellular signaling pathways. In one context, SOCS7 acts as an adaptor protein bearing nuclear import and export signals; it mediates the shuttling of proteins such as NCK from the cytoplasm to the nucleus, a process that is critical for maintaining cytoskeletal integrity and coordinating the DNA damage response, including p53 Ser15 phosphorylation. In addition, SOCS7 directly interferes with cytokine-driven signals by binding to activated STAT3 and STAT5—thereby blocking their phosphorylation and subsequent nuclear translocation in response to prolactin, growth hormone, or leptin stimulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cytokine signaling, SOCS7 critically modulates metabolic pathways. Studies in Socs7-deficient mice have shown enhanced insulin action, with increased insulin receptor substrate (IRS) protein levels leading to improved glucose clearance and lower fasting glucose concentrations. In related cellular models, SOCS7 has been shown to interact directly with the insulin receptor and IRS1, thereby serving as a negative regulator of insulin signaling. Furthermore, in the setting of hepatitis C virus infection, SOCS7 expression is upregulated through mechanisms independent of STAT3—being instead influenced by peroxisome proliferator-activated receptor gamma (PPAR‑γ)—and by interactions with noncoding RNAs that sponge regulatory microRNAs. These findings underscore the importance of SOCS7 in insulin resistance and glucose homeostasis, with genetic variants in SOCS7 also being linked to metabolic traits."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSOCS7 also plays diverse roles in oncogenesis and tumor progression. In breast cancer cells, knockdown experiments have revealed that SOCS7 modulates the growth and migration of tumor cells by interacting with phospholipase Cγ‑1, a key downstream effector of both the insulin‐like growth factor‑I and hepatocyte growth factor/C‑MET axes. In bladder cancer models, SOCS7 appears to function as an oncogene by influencing interferon‑β signaling and the nuclear translocation of STAT3; its downregulation by miR‑145 leads to increased IFN‑β induction and caspase‑dependent apoptosis. Moreover, in hepatocellular carcinoma, SOCS7 exhibits E3 ubiquitin ligase activity toward the adaptor protein Shc1 and has been implicated in the reduction of immunosuppressive factors, thereby inhibiting STAT3 activation and tumor growth. Differential expression studies in breast cancer tissues further support a role for SOCS7 in tumor biology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in signal transduction and metabolism, SOCS7 is involved in modulating cytoskeletal dynamics and cellular differentiation. A yeast two‑hybrid screen identified vinexin—a cytoskeletal adaptor protein—as a binding partner of SOCS7, with the interaction mediated via a proline‑rich motif within SOCS7. This association suggests that SOCS7 may contribute to the spatial organization of the actin cytoskeleton. Moreover, a peptide derived from the BC‑box motif of SOCS7 has been shown to induce cholinergic differentiation in adipose‑derived mesenchymal stem cells, pointing to potential applications in regenerative medicine for neurodegenerative disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther studies have further expanded the functional landscape of SOCS7. Increased SOCS7 protein levels have been noted in brain tissue from patients with Alzheimer’s disease, suggesting a role in modulating neuroinflammatory responses. Likewise, polymorphism studies have implicated SOCS7 in the pathogenesis of psoriasis, and its involvement in neuroendocrine differentiation has been examined in prostate cancer models. These diverse findings reinforce the view that SOCS7 is an important regulatory molecule with multifaceted roles spanning immune regulation, metabolism, cancer biology, and neuronal differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brandon E Kremer, Laura A Adang, Ian G Macara "}, {"type": "b", "children": [{"type": "t", "text": "Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2007.06.053"}], "href": "https://doi.org/10.1016/j.cell.2007.06.053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17803907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17803907"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nele Martens, Galit Uzan, Maxime Wery, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation."}]}, {"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.M411596200"}], "href": "https://doi.org/10.1074/jbc.M411596200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15677474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15677474"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Alexander S Banks, Jianze Li, Lisa McKeag, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI23853"}], "href": "https://doi.org/10.1172/JCI23853"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16127460"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16127460"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Valerio Pazienza, Manlio Vinciguerra, Angelo Andriulli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatitis C virus core protein genotype 3a increases SOCS-7 expression through PPAR-{gamma} in Huh-7 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gen Virol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1099/vir.0.020644-0"}], "href": "https://doi.org/10.1099/vir.0.020644-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20357037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20357037"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Melissa M Capuano, John D Sorkin, Yen-Pei C Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in the SOCS7 gene and glucose homeostasis traits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Res Notes (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1756-0500-6-235"}], "href": "https://doi.org/10.1186/1756-0500-6-235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23767996"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23767996"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "M L Tellechea, A Penas Steinhardt, G Rodriguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variants in SOCS7 gene predict obesity, disturbances in lipid metabolism and insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nutr Metab Cardiovasc Dis (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.numecd.2011.10.005"}], "href": "https://doi.org/10.1016/j.numecd.2011.10.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22397880"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22397880"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Haiyan Zeng, Lei Li, Yi Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA UCA1 regulates HCV replication and antiviral response via miR-145-5p/SOCS7/IFN pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.59227"}], "href": "https://doi.org/10.7150/ijbs.59227"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34345210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34345210"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "W Sasi, L Ye, W G Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Observations on the effects of Suppressor of Cytokine Signaling 7 (SOCS7) knockdown in breast cancer cells: their in vitro response to Insulin Like Growth Factor I (IGF-I)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Transl Oncol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12094-013-1107-0"}], "href": "https://doi.org/10.1007/s12094-013-1107-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24046004"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24046004"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Walid Sasi, Lin Ye, Wen G Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vitro and in vivo effects of suppressor of cytokine signalling 7 knockdown in breast cancer: the influence on cellular response to hepatocyte growth factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2014/648040"}], "href": "https://doi.org/10.1155/2014/648040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25162020"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25162020"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "S Noguchi, N Yamada, M Kumazaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "socs7, a target gene of microRNA-145, regulates interferon-β induction through STAT3 nuclear translocation in bladder cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2013.11"}], "href": "https://doi.org/10.1038/cddis.2013.11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23392170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23392170"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Peixin Huang, Zhiying Zhao, Yi Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The E3 ubiquitin ligase SOCS-7 reverses immunosuppression via Shc1 signaling in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41374-022-00727-5"}], "href": "https://doi.org/10.1038/s41374-022-00727-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35042950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35042950"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Walid Sasi, Wen G Jiang, Anup Sharma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-10-178"}], "href": "https://doi.org/10.1186/1471-2407-10-178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20433750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20433750"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Nele Martens, Maxime Wery, Ping Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The suppressor of cytokine signaling (SOCS)-7 interacts with the actin cytoskeleton through vinexin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2004.04.002"}], "href": "https://doi.org/10.1016/j.yexcr.2004.04.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15242778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15242778"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hiroshi Kanno, Shutaro Matsumoto, Tetsuya Yoshizumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOCS7-Derived BC-Box Motif Peptide Mediated Cholinergic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms24032786"}], "href": "https://doi.org/10.3390/ijms24032786"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36769102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36769102"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "D G Walker, A M Whetzel, L-F Lue "}, {"type": "b", "children": [{"type": "t", "text": "Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer's disease brains and human microglia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroscience (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroscience.2014.09.052"}], "href": "https://doi.org/10.1016/j.neuroscience.2014.09.052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25286386"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25286386"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Merve Özçep, Nilhan Atsü, Nilgün Solak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of association between SOCS3 and SOCS7 polymorphisms and psoriasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immun Inflamm Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iid3.695"}], "href": "https://doi.org/10.1002/iid3.695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36169255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36169255"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Dongxia Ge, Allen C Gao, Qiuyang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LNCaP prostate cancer cells with autocrine interleukin-6 expression are resistant to IL-6-induced neuroendocrine differentiation due to increased expression of suppressors of cytokine signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.22479"}], "href": "https://doi.org/10.1002/pros.22479"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22213096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22213096"}]}]}]}