{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have shed light on two seemingly distinct cellular processes: chromatin regulation by the male‐specific lethal (MSL) complex and vesicular trafficking at the trans‐Golgi network (TGN). Investigations into the MSL complex have revealed its role in dosage compensation and transcriptional regulation during development, as illustrated by work on the structural interactions among MSL subunits (for example, in the context of MSL1 scaffolding and the modulation of H4K16 acetylation)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In contrast, a separate line of inquiry has focused on the assembly of the adaptor protein complex 4 (AP-4) coat, where the accessory protein tepsin plays a pivotal role.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTepsin, an ENTH/VHS-domain-containing protein, has been identified as an essential accessory component for AP-4 function at the TGN. Detailed protein interaction studies have revealed that tepsin harbors two phylogenetically conserved peptide motifs within its C-terminal disordered region. These motifs specifically engage the C-terminal ear (appendage) domains of the AP-4 β4 and ε subunits, respectively. The bivalent interactions mediated by these short linear motifs not only secure tepsin’s recruitment to the TGN but also likely contribute to the cross-linking of multiple AP-4 heterotetramers, thus promoting the efficient assembly of a non-clathrin coat essential for proper protein sorting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, while studies on the MSL complex underscore the intricacies of transcriptional regulation and chromatin modification"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ", research on tepsin reveals its specialized role in vesicular trafficking. By employing bivalent peptide-ear interactions that secure its association with the AP-4 coat, tepsin functions as a critical scaffold that facilitates coat assembly and the subsequent sorting of cargo proteins at the TGN.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jan Kadlec, Erinc Hallacli, Michael Lipp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1960"}], "href": "https://doi.org/10.1038/nsmb.1960"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21217699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21217699"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "An Ye, Hana Kim, Joomyeong Kim "}, {"type": "b", "children": [{"type": "t", "text": "PEG3 control on the mammalian MSL complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0178363"}], "href": "https://doi.org/10.1371/journal.pone.0178363"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28609438"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28609438"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "T A Mitchell, J M Lin, S M Hicks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of function of male-specific lethal 3 (Msl3) does not affect spermatogenesis in rodents."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.669"}], "href": "https://doi.org/10.1002/dvdy.669"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37847071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37847071"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rafael Mattera, Carlos M Guardia, Sachdev S Sidhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bivalent Motif-Ear Interactions Mediate the Association of the Accessory Protein Tepsin with the AP-4 Adaptor Complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.683409"}], "href": "https://doi.org/10.1074/jbc.M115.683409"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26542808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26542808"}]}]}]}