生物谷報道：PLK1(polo-like kinase)是有絲分裂必需的蛋白,，它對于保證染色體正常分離具有關(guān)鍵的作用,。然而,，PLK1是如何募集到著絲粒上的,，以及募集后的位點作用機(jī)制,，目前并不十分清楚。最近,，美國和韓國的科學(xué)家共同發(fā)現(xiàn)了一種新的蛋白在PLK1的募集過程中起重要作用,，即PBIP1蛋白。該結(jié)果發(fā)表于最新一期的《molecular cell》上,。
這項研究的結(jié)果發(fā)現(xiàn),，PBIP1，即PBD結(jié)合蛋白(PBD binding protein),，可以與PLK1的PBD結(jié)構(gòu)域結(jié)合,并將之募集到著絲粒上,。PLK1通過磷酸化PBIP1的78位Thr,，使之形成可與自身PBD結(jié)構(gòu)域結(jié)合的位點.同時確保其不與PLK2,PLK3結(jié)合,。而在有絲分裂的稍后階段,，PLK1同樣通過對T78的位點的作用,使PBIP1降解,，使自己可以與涉及著絲粒功能的其他蛋白結(jié)合,。相反,，通過T78位磷酸化作用募集的PLK1如果缺失,，會導(dǎo)致染色體凝集缺陷,，有絲分裂的紡錘體檢驗點異常,，最終導(dǎo)致非整倍體,。
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.
這一發(fā)現(xiàn)證實了PIK1通過與PBIP1的作用自體調(diào)節(jié)，并在有絲分裂中正確的時間點募集到著絲粒上,，促進(jìn)染色體正常分離,。這也將大大地有利于進(jìn)一步研究PIK1蛋白在有絲分裂調(diào)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,。
全文下載：pdf supplemental data
相關(guān)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
相關(guān)報道：
著絲粒的異染色質(zhì)區(qū)對黏附的作用
《任小二快報》：著絲粒的秘密
