CDK1-cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry.
CDK1-cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry.
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CDK1-CYCLIN-B1诱导的Kindlin降解在有丝分裂进入时脱离了局灶性粘附。
DOI：
10.1038/s41556-022-00886-z
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发表时间：
2022-05
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
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在有丝分裂进入时，含有整合素的粘着斑（FA）的解体对于细胞变圆、有丝分裂回缩纤维形成、双极纺锤体定位和染色体分离是必不可少的。在有丝分裂进入时驱动FA分解的机制尚不清楚。在这里，我们表明，CDK 1-细胞周期蛋白B1复合物磷酸化的整合素激活剂kindlin，这导致在招聘的cullin 9-FBXL 10泛素连接酶复合物介导kindlin泛素化和降解。这种分子途径对于FA分解和细胞变圆是必不可少的，因为CDK 1基序的磷酸化抑制突变阻止了Kindlin降解、FA分解和有丝分裂细胞变圆。相反，磷酸模拟突变促进kindlin降解间期，加速有丝分裂细胞变圆和损害有丝分裂收缩纤维的形成。尽管对kindlin稳定性有相反的影响，但这两种类型的突变都会导致严重的有丝分裂纺锤体缺陷、细胞凋亡和非整倍体。因此，有丝分裂进入时kindlin水平的精确调节对于细胞准确地通过有丝分裂是必不可少的。Chen等报道，在有丝分裂进入时，细胞周期蛋白B1-CDK 1磷酸化粘着斑蛋白kindlin，诱导其蛋白酶体降解，并促进粘着斑解体和有丝分裂变圆。
The disassembly of integrin-containing focal adhesions (FAs) at mitotic entry is essential for cell rounding, mitotic retraction fibre formation, bipolar spindle positioning and chromosome segregation. The mechanism that drives FA disassembly at mitotic entry is unknown. Here, we show that the CDK1–cyclin B1 complex phosphorylates the integrin activator kindlin, which results in the recruitment of the cullin 9–FBXL10 ubiquitin ligase complex that mediates kindlin ubiquitination and degradation. This molecular pathway is essential for FA disassembly and cell rounding, as phospho-inhibitory mutations of the CDK1 motif prevent kindlin degradation, FA disassembly and mitotic cell rounding. Conversely, phospho-mimetic mutations promote kindlin degradation in interphase, accelerate mitotic cell rounding and impair mitotic retraction fibre formation. Despite the opposing effects on kindlin stability, both types of mutations cause severe mitotic spindle defects, apoptosis and aneuploidy. Thus, the exquisite regulation of kindlin levels at mitotic entry is essential for cells to progress accurately through mitosis. Chen et al. report that at mitotic entry, cyclin B1–CDK1 phosphorylates the focal adhesion protein kindlin to induce its proteasomal degradation and promote focal adhesion disassembly and mitotic rounding.
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影响因子：
7.3
作者：
Alexander J;Lim D;Joughin BA;Hegemann B;Hutchins JR;Ehrenberger T;Ivins F;Sessa F;Hudecz O;Nigg EA;Fry AM;Musacchio A;Stukenberg PT;Mechtler K;Peters JM;Smerdon SJ;Yaffe MB
通讯作者：
Yaffe MB
DOI：
10.1083/jcb.201701176
发表时间：
2017-11-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Böttcher RT;Veelders M;Rombaut P;Faix J;Theodosiou M;Stradal TE;Rottner K;Zent R;Herzog F;Fässler R
通讯作者：
Fässler R
F-box蛋白家族。
影响因子：
12.3
作者：
Kipreos, E T;Pagano, M
通讯作者：
Pagano, M
影响因子：
16.8
作者：
Koivomaegi, Mardo;Oerd, Mihkel;Iofik, Anna;Valk, Ervin;Venta, Rainis;Faustova, Ilona;Kivi, Rait;Balog, Eva Rose M.;Rubin, Seth M.;Loog, Mart
通讯作者：
Loog, Mart
影响因子：
4
作者：
Humphries JD;Byron A;Humphries MJ
通讯作者：
Humphries MJ