生物谷报道:PLK1(polo-like kinase)是有丝分裂必需的蛋白,它对于保证染色体正常分离具有关键的作用。然而,PLK1是如何募集到着丝粒上的,以及募集后的位点作用机制,目前并不十分清楚。最近,美国和韩国的科学家共同发现了一种新的蛋白在PLK1的募集过程中起重要作用,即PBIP1蛋白。该结果发表于最新一期的《molecular cell》上。
这项研究的结果发现,PBIP1,即PBD结合蛋白(PBD binding protein),可以与PLK1的PBD结构域结合,并将之募集到着丝粒上。PLK1通过磷酸化PBIP1的78位Thr,使之形成可与自身PBD结构域结合的位点.同时确保其不与PLK2,PLK3结合。而在有丝分裂的稍后阶段,PLK1同样通过对T78的位点的作用,使PBIP1降解,使自己可以与涉及着丝粒功能的其他蛋白结合。相反,通过T78位磷酸化作用募集的PLK1如果缺失,会导致染色体凝集缺陷,有丝分裂的纺锤体检验点异常,最终导致非整倍体。
Figure 1. PBIP1 Interacts and Colocalizes with Plk1 at the Interphase and Mitotic Kinetochores
(A) Physical interaction between PBIP1 and Plk1 in HeLa cells. Cells transfected with either the full-length PBIP1 or HA-Plk1 were loaded to mark the position of PBIP1 and Plk1. Preimm., preimmune serum. Arrows, tiers of modified PBIP1 species generated after transfection; asterisk, a crossreacting band.
(B) PBIP1-Flag was immunoprecipitated from transfected HeLa cells. Arrows, immunoprecipitated multiple PBIP1 species.
(C) Cells were costained with the indicated antibodies. Arrowheads, centrosomes; asterisks, interphase PBIP1 signals.
这一发现证实了PIK1通过与PBIP1的作用自体调节,并在有丝分裂中正确的时间点募集到着丝粒上,促进染色体正常分离。这也将大大地有利于进一步研究PIK1蛋白在有丝分裂调控中的作用。
原文引用:
Molecular cell Volume 24, Issue 3 , 3 November 2006, Pages 409-422
Self-Regulated Plk1 Recruitment to Kinetochores by the Plk1-PBIP1 Interaction Is Critical for Proper Chromosome Segregation
Young H. Kang etal
Abstract:
The polo-box domain (PBD) of mammalian polo-like kinase 1 (Plk1) is essential in targeting its catalytic activity to specific subcellular structures critical for mitosis. The mechanism underlying Plk1 recruitment to the kinetochores and the role of Plk1 at this site remain elusive. Here, we demonstrate that a PBD-binding protein, PBIP1, is crucial for recruiting Plk1 to the interphase and mitotic kinetochores. Unprecedentedly, Plk1 phosphorylated PBIP1 at T78, creating a self-tethering site that specifically interacted with the PBD of Plk1, but not Plk2 or Plk3. Later in mitosis, Plk1 also induced PBIP1 degradation in a T78-dependent manner, thereby enabling itself to interact with other components critical for proper kinetochore functions. Absence of the p-T78-dependent Plk1 localization induced a chromosome congression defect and compromised the spindle checkpoint, ultimately leading to aneuploidy. Thus, Plk1 self-regulates the Plk1-PBIP1 interaction to timely localize to the kinetochores and promote proper chromosome segregation。
全文下载:pdf supplemental data
相关基因 Pubmed gene:
Official Symbol: PLK1 and Name: polo-like kinase 1 (Drosophila) [Homo sapiens]
Other Aliases: PLK, STPK13
Other Designations: cell cycle regulated protein kinase; polo (Drosophia)-like kinase;
polo like kinase; polo-like kinase; polo-like kinase (Drosophila)
Chromosome: 16; Location: 16p12.1
MIM: 602098
GeneID: 5347
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着丝粒的异染色质区对黏附的作用
《任小二快报》:着丝粒的秘密