{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DYNLL1, also known as LC8, is a highly conserved dynein light chain that functions as a versatile adaptor and regulatory hub linking the microtubule motor machinery to diverse cellular processes. In the context of apoptosis and autophagy, DYNLL1 binds the pro‐apoptotic protein Bim and helps sequester it in an inactive state by bridging its interaction with Beclin 1; upon specific phosphorylation signals triggered by cellular stress, this complex dissociates allowing Bim to promote mitochondria‐dependent apoptosis and relieve its inhibitory effect on autophagy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, DYNLL1 plays a critical role in the maintenance of genomic stability by associating directly with components of the DNA end‐resection machinery. Binding to MRE11, DYNLL1 limits nucleolytic degradation at DNA double‐strand breaks; consequently, loss of DYNLL1 permits enhanced DNA end resection, restores homologous recombination in BRCA1‐deficient cells, and modulates responses to DNA‐damaging therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond genome maintenance, DYNLL1 contributes to the regulation of cytoskeletal dynamics and signal transduction. It directly interacts with signaling mediators such as RASGRP1 to link receptor‐triggered events with cytoskeletal rearrangements and RhoA activation, thereby influencing lymphocyte activation, proliferation, and motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " During mitosis, DYNLL1 becomes specifically recruited via partners (e.g. through TQT motifs in CHICA) to mediate the asymmetric cortical localization of dynein, an essential step ensuring correct spindle orientation and accurate cell division."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, DYNLL1 facilitates the nuclear import of Pak1 by promoting its dimerization, a mechanism that is required for proper signal transduction and normal vertebrate development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Acting as a broad‐spectrum “dimerization engine,” DYNLL1 recognizes conserved linear peptide motifs within an array of target proteins. Its own cellular levels are tightly regulated by factors such as ASCIZ, which both activates Dynll1 gene expression and is inhibited by DYNLL1 in a feedback loop—a system that enables the fine tuning of numerous dynein‐dependent processes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, DYNLL1 is implicated in ciliary function by contributing to the assembly and regulation of the intraflagellar transport (IFT) dynein motor. Its interaction with components such as WDR34 suggests that DYNLL1 may help coordinate retrograde ciliary trafficking that is essential for proper ciliogenesis and signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings reveal that DYNLL1 serves as an essential molecular adaptor linking dynein motor activity to cellular pathways that regulate apoptosis, DNA repair, cell signaling, mitotic spindle orientation, and ciliary dynamics.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shouqing Luo, Moises Garcia-Arencibia, Rui Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bim inhibits autophagy by recruiting Beclin 1 to microtubules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2012.05.040"}], "href": "https://doi.org/10.1016/j.molcel.2012.05.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22742832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22742832"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yizhou Joseph He, Khyati Meghani, Marie-Christine Caron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DYNLL1 binds to MRE11 to limit DNA end resection in BRCA1-deficient cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-018-0670-5"}], "href": "https://doi.org/10.1038/s41586-018-0670-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30464262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30464262"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Elisabeth Salzer, Deniz Cagdas, Miroslav Hons, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.3575"}], "href": "https://doi.org/10.1038/ni.3575"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27776107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27776107"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anja K Dunsch, Dean Hammond, Jennifer Lloyd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynein light chain 1 and a spindle-associated adaptor promote dynein asymmetry and spindle orientation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201202112"}], "href": "https://doi.org/10.1083/jcb.201202112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22965910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22965910"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Christine M Lightcap, Gabor Kari, Luis E Arias-Romero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction with LC8 is required for Pak1 nuclear import and is indispensable for zebrafish development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0006025"}], "href": "https://doi.org/10.1371/journal.pone.0006025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19557173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19557173"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sabine Jurado, Lindus A Conlan, Emma K Baker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATM substrate Chk2-interacting Zn2+ finger (ASCIZ) Is a bi-functional transcriptional activator and feedback sensor in the regulation of dynein light chain (DYNLL1) expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.306019"}], "href": "https://doi.org/10.1074/jbc.M111.306019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22167198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22167198"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Péter Rapali, László Radnai, Dániel Süveges, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Directed evolution reveals the binding motif preference of the LC8/DYNLL hub protein and predicts large numbers of novel binders in the human proteome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0018818"}], "href": "https://doi.org/10.1371/journal.pone.0018818"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21533121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21533121"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Miriam Schmidts, Julia Vodopiutz, Sonia Christou-Savina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the gene encoding IFT dynein complex component WDR34 cause Jeune asphyxiating thoracic dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2013.10.003"}], "href": "https://doi.org/10.1016/j.ajhg.2013.10.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24183451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24183451"}]}]}]}