Plk1-mediated mitotic phosphorylation of PinX1 regulates its stability.
PinX1 was originally identified as a Pin2/TRF1-interacting protein that suppresses telomerase activity via its telomerase inhibitor domain (TID) and regulates the nucleolar localization of TRF1 in telomerase-positive cells. In addition to its telomeric localization, PinX1 can be found in the nucleoli of human cells. Our recent studies have shown that PinX1 localizes to the chromosome periphery and kinetochores in mitosis. Depletion of PinX1 results in lagging chromosomes in mitosis and micronuclei in interphase. However, less is known about the post-translational modification of PinX1 in mitosis. Here, we show that Polo-like kinase 1 (Plk1) is a novel interacting protein of PinX1. Plk1 interacts with and phosphorylates PinX1 in vivo and in vitro. Overexpression of Plk1 promotes protein turnover of PinX1, a process that depends on ubiquitin-associated proteasomal degradation. Depletion of Plk1 using siRNA increases the stability of PinX1 at protein level in mitosis. Moreover, Plk1-mediated phosphorylation of PinX1 at five phosphorylation sites is essential for its Plk1-induced degradation. These findings suggest that Plk1 may negatively regulate the stability of PinX1 by mitotic phosphorylation.
Wang
Chong
C
The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China.
Yu
Jian
J
Yuan
Kai
K
Lan
Jianping
J
Jin
Changjiang
C
Huang
He
H
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C440808:PINX1 protein, human