{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe body of work summarized here characterizes a kinesin‐2–associated protein—functionally analogous to what has been termed MGAM2 in this context—as a pivotal adaptor that orchestrates microtubule‐dependent cargo transport in diverse cellular settings. Disruption of its capacity to bind the kinesin motor subunits during mitosis leads to defective spindle formation and chromosomal mis‐segregation, underscoring its critical role in cell division."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn differentiated cells, aberrant interactions of this protein further contribute to disease pathogenesis. In a model of familial amyotrophic lateral sclerosis, misfolded SOD1 species sequester the adaptor protein, thereby impairing the microtubule‐dependent transport of choline acetyltransferase and ultimately compromising synaptic function in motor neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, studies in hematological malignancy have highlighted that alterations in chromatin‐binding motifs—illustrated by the analysis of a NUP98‐PHF23 fusion protein—can disturb gene expression programs that may intersect with the broader regulatory networks of intracellular transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, during early neuronal development this microtubule‐based transport is exquisitely regulated to specify axonal identity. A phosphorylation cascade mediated by MARK2 governs the binding of the motor complex to cargos such as TRIM46, ensuring their selective delivery to the axon initial segment—a process essential for establishing and maintaining neuronal polarity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Keiko Haraguchi, Tomoatsu Hayashi, Takeshi Jimbo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of the kinesin-2 family protein, KIF3, during mitosis."}]}, {"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.M507028200"}], "href": "https://doi.org/10.1074/jbc.M507028200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16298999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16298999"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Minako Tateno, Shinsuke Kato, Takashi Sakurai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant SOD1 impairs axonal transport of choline acetyltransferase and acetylcholine release by sequestering KAP3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddn422"}], "href": "https://doi.org/10.1093/hmg/ddn422"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19088126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19088126"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sheryl M Gough, Fan Lee, Fan Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NUP98-PHF23 is a chromatin-modifying oncoprotein that causes a wide array of leukemias sensitive to inhibition of PHD histone reader function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-13-0419"}], "href": "https://doi.org/10.1158/2159-8290.CD-13-0419"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24535671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24535671"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sotaro Ichinose, Tadayuki Ogawa, Xuguang Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Spatiotemporal Construction of the Axon Initial Segment via KIF3/KAP3/TRIM46 Transport under MARK2 Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.07.093"}], "href": "https://doi.org/10.1016/j.celrep.2019.07.093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31461655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31461655"}]}]}]}