Pharmaceutical Sciences Faculty Publications

Self-Regulated Plk1 Recruitment to Kinetochores by the Plk1-PBIP1 Interaction is Critical for Proper Chromosome Segregation

Document Type

Article

Publication Date

11-3-2006

Journal Title

Molecular Cell

ISSN

1097-2765

Volume

24

Issue

3

First Page

409

Last Page

422

DOI

10.1016/j.molcel.2006.10.016

PubMed ID

17081991

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.

Keywords

Amino acid motifs, amino acid sequence, carrier proteins, cell cycle proteins, chromosome segregation, epitopes, kinetochores, biological, phosphorylation, prometaphase, prophase, protein binding, protein processing, tertiary, proteins, proto-oncogene proteins, serine, threonine

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