mitotic spindle assembly checkpoint MAD1-MAD2 complex / metaphase/anaphase transition of cell cycle / metaphase/anaphase transition of meiosis I / Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components / mitotic checkpoint complex / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of mitotic cell cycle spindle assembly checkpoint / establishment of centrosome localization / regulation of meiotic nuclear division / positive regulation of synapse maturation ...mitotic spindle assembly checkpoint MAD1-MAD2 complex / metaphase/anaphase transition of cell cycle / metaphase/anaphase transition of meiosis I / Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components / mitotic checkpoint complex / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of mitotic cell cycle spindle assembly checkpoint / establishment of centrosome localization / regulation of meiotic nuclear division / positive regulation of synapse maturation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / meiotic sister chromatid cohesion, centromeric / regulation of dendrite development / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / positive regulation of synaptic plasticity / Phosphorylation of Emi1 / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / protein branched polyubiquitination / metaphase/anaphase transition of mitotic cell cycle / regulation of meiotic cell cycle / anaphase-promoting complex-dependent catabolic process / Phosphorylation of the APC/C / regulation of exit from mitosis / anaphase-promoting complex binding / nuclear pore nuclear basket / outer kinetochore / protein localization to chromosome, centromeric region / positive regulation of mitotic metaphase/anaphase transition / positive regulation of dendrite morphogenesis / positive regulation of ubiquitin protein ligase activity / ubiquitin ligase activator activity / protein K11-linked ubiquitination / regulation of mitotic metaphase/anaphase transition / ubiquitin-ubiquitin ligase activity / mitotic sister chromatid cohesion / mitotic metaphase chromosome alignment / negative regulation of ubiquitin protein ligase activity / mitotic spindle assembly checkpoint signaling / Regulation of APC/C activators between G1/S and early anaphase / establishment of mitotic spindle orientation / cullin family protein binding / mitotic sister chromatid segregation / Transcriptional Regulation by VENTX / negative regulation of mitotic cell cycle / mitotic spindle assembly / enzyme-substrate adaptor activity / ubiquitin-like ligase-substrate adaptor activity / positive regulation of axon extension / protein K48-linked ubiquitination / heterochromatin / intercellular bridge / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / nuclear periphery / Resolution of Sister Chromatid Cohesion / regulation of mitotic cell cycle / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / SCF-beta-TrCP mediated degradation of Emi1 / Assembly of the pre-replicative complex / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / RHO GTPases Activate Formins / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / brain development / negative regulation of protein catabolic process / kinetochore / CDK-mediated phosphorylation and removal of Cdc6 / spindle / histone deacetylase binding / spindle pole / neuron projection development / ubiquitin-protein transferase activity / mitotic spindle / Separation of Sister Chromatids / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / nervous system development / mitotic cell cycle / microtubule cytoskeleton / Senescence-Associated Secretory Phenotype (SASP) / ubiquitin-dependent protein catabolic process / protein phosphatase binding / molecular adaptor activity / cell differentiation / non-specific serine/threonine protein kinase / protein kinase activity / Ub-specific processing proteases / protein ubiquitination / ciliary basal body / negative regulation of gene expression / cell division / protein serine kinase activity / protein serine/threonine kinase activity / intracellular membrane-bounded organelle 類似検索 - 分子機能
ジャーナル: EMBO Rep / 年: 2020 タイトル: A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase. 著者: Claudio Alfieri / Thomas Tischer / David Barford / 要旨: The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of ...The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of the APC/C in mitosis is restrained by the spindle assembly checkpoint (SAC), which coordinates chromosome segregation with the assembly of the mitotic spindle. The SAC effector is the mitotic checkpoint complex (MCC), which binds and inhibits the APC/C. It is incompletely understood how the APC/C switches substrate specificity in a cell cycle-specific manner. For instance, it is unclear how in prometaphase, when APC/C activity towards cyclin B and securin is repressed by the MCC, the kinase Nek2A is ubiquitinated. Here, we combine biochemical and structural analysis with functional studies in cells to show that Nek2A is a conformational-specific binder of the APC/C-MCC complex (APC/C ) and that, in contrast to cyclin A, Nek2A can be ubiquitinated efficiently by the APC/C in conjunction with both the E2 enzymes UbcH10 and UbcH5. We propose that these special features of Nek2A allow its prometaphase-specific ubiquitination.