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Structure of Chromosomal Passenger Complex (CPC) bound to phosphorylated Histone 3 peptide at 1.8 A.Structure of Chromosomal Passenger Complex (CPC) bound to phosphorylated Histone 3 peptide at 1.8 A.
Structural highlights
FunctionBIRC5_HUMAN Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis. Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules. The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Isoform 2 and isoform 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform.[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedThe Aurora B chromosomal passenger complex (CPC) is a conserved regulator of mitosis. Its functions require localization first to the chromosome arms and then centromeres in mitosis and subsequently the central spindle in anaphase. Here, we analyze the requirements for core CPC subunits, survivin and INCENP, and the mitotic kinesin-like protein 2 (MKLP2) in targeting to these distinct localizations. Centromere recruitment of the CPC requires interaction of survivin with histone H3 phosphorylated at threonine 3, and we provide a complete structure of this assembly. Furthermore, we show that the INCENP RRKKRR-motif is required for both centromeric localization of the CPC in metaphase and MKLP2-dependent transport in anaphase. MKLP2 and DNA bind competitively to this motif, and INCENP T59 phosphorylation acts as a switch preventing MKLP2 binding in metaphase. In anaphase, CPC binding promotes the microtubule-dependent ATPase activity of MKLP2. These results explain how centromere targeting of the CPC in mitosis is coupled to its movement to the central spindle in anaphase. Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle.,Serena M, Bastos RN, Elliott PR, Barr FA J Cell Biol. 2020 Jul 6;219(7). pii: 151730. doi: 10.1083/jcb.201910059. PMID:32356865[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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