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 ubiquitin protein ligase activity / negative regulation of ubiquitin protein ligase activity / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of synapse maturation / regulation of meiotic nuclear division ...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 ubiquitin protein ligase activity / negative regulation of ubiquitin protein ligase activity / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of synapse maturation / regulation of meiotic nuclear division / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / meiotic sister chromatid cohesion, centromeric / positive regulation of mitotic cell cycle spindle assembly checkpoint / regulation of dendrite development / anaphase-promoting complex / Phosphorylation of Emi1 / Aberrant regulation of mitotic exit in cancer due to RB1 defects / anaphase-promoting complex-dependent catabolic process / regulation of meiotic cell cycle / protein branched polyubiquitination / metaphase/anaphase transition of mitotic cell cycle / Phosphorylation of the APC/C / anaphase-promoting complex binding / protein localization to chromosome, centromeric region / regulation of exit from mitosis / nuclear pore nuclear basket / outer kinetochore / positive regulation of synaptic plasticity / positive regulation of dendrite morphogenesis / positive regulation of mitotic metaphase/anaphase transition / negative regulation of mitotic cell cycle / protein K11-linked ubiquitination / ubiquitin ligase activator activity / regulation of mitotic metaphase/anaphase transition / mitotic sister chromatid cohesion / ubiquitin-ubiquitin ligase activity / mitotic metaphase chromosome alignment / mitotic spindle assembly checkpoint signaling / Regulation of APC/C activators between G1/S and early anaphase / Transcriptional Regulation by VENTX / mitotic sister chromatid segregation / mitotic spindle assembly / cullin family protein binding / enzyme-substrate adaptor activity / positive regulation of axon extension / intercellular bridge / ubiquitin-like ligase-substrate adaptor activity / heterochromatin / protein K48-linked ubiquitination / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / nuclear periphery / APC/C:Cdc20 mediated degradation of Cyclin B / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / regulation of mitotic cell cycle / APC-Cdc20 mediated degradation of Nek2A / Resolution of Sister Chromatid Cohesion / 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 / negative regulation of protein catabolic process / brain development / G protein-coupled receptor binding / 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 / nervous system development / Antigen processing: Ubiquitination & Proteasome degradation / mitotic cell cycle / microtubule cytoskeleton / Senescence-Associated Secretory Phenotype (SASP) / protein phosphatase binding / molecular adaptor activity / ubiquitin-dependent protein catabolic process / cell differentiation / protein kinase activity / non-specific serine/threonine protein kinase / Ub-specific processing proteases / ciliary basal body / protein ubiquitination / negative regulation of gene expression / cell division / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / positive regulation of cell population proliferation 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.