Dynamic regulation of ubiquitylation and deubiquitylation at the central spindle during cytokinesis

Dynamic regulation of ubiquitylation and deubiquitylation at the central spindle during cytokinesis
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DOI:
10.1242/jcs.027417
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发表时间:
2008-04-15
影响因子:
4
通讯作者:
Komada, Masayuki
Komada, Masayuki
中科院分区:
生物学2区
文献类型:
--
作者:
Mukai, Akiko;Mizuno, Emi;Komada, Masayuki

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在胞质分裂过程中,中央纺锤体(位于分离染色体之间的一束相互交叉的反平行微管)将各种细胞分裂调节蛋白募集到裂解区域。在这里,我们发现在胞质分裂过程中,中央纺锤体 Aurora B 激酶阳性双带区域的蛋白质泛素化水平显着且短暂地升高。两种在间期作用于内体的去泛素化酶 UBPY 和 AMSH 也被招募到裂解区域。 UBPY 仅在胞质分裂的最后阶段在中体检测到,而 AMSH 在整个胞质分裂过程中定位于围绕中央纺锤体和中体有丝分裂驱动蛋白 MKLP1 阳性区域的环状结构。细胞 UBPY 或 AMSH 的消耗导致胞质分裂缺陷。 VAMP8 是胞质分裂中囊泡融合所需的 v-SNARE,定位于泛素化蛋白呈阳性的中央纺锤体区域,并经历 UBPY 和 AMSH 的泛素化和去泛素化。因此,我们的结果暗示了胞质分裂中包括 VAMP8 在内的蛋白质的泛素化/去泛素化。
During cytokinesis, the central spindle, a bundle of interdigitated anti-parallel microtubules between separating chromosomes, recruits various cytokinetic regulator proteins to the cleavage region. Here, we show that the level of protein ubiquitylation is strikingly and transiently elevated in Aurora B kinase-positive double-band regions of the central spindle during cytokinesis. Two deubiquitylating enzymes UBPY and AMSH, which act on endosomes in interphase, were also recruited to the cleavage region. Whereas UBPY was detected only in the final stage of cytokinesis at the midbody, AMSH localized to a ring structure surrounding the mitotic kinesin MKLP1-positive region of the central spindle and midbody throughout cytokinesis. Depletion of cellular UBPY or AMSH led to defects in cytokinesis. VAMP8, a v-SNARE required for vesicle fusion in cytokinesis, localized to the central spindle region positive for ubiquitylated proteins, and underwent ubiquitylation and deubiquitylation by both UBPY and AMSH. Our results thus implicate the ubiquitylation/deubiquitylation of proteins including VAMP8 in cytokinesis.