Sirt1 Regulates Microtubule Dynamics Through Negative Regulation of Plk1 in Mitosis.
Although loss of Sirt1 leads to chromosome aneuploidy, which accounts for higher tumor susceptibility, the molecular mechanisms remain unclear. Herein, we demonstrate that Sirt1 directly regulates Plk1, of which activity is critical for mitotic progression and spindle dynamics. Depletion or inhibition of Sirt1 significantly perturbs the formation of the mitotic spindle, leading to defective chromosome segregation. Elevated depolymerization of the mitotic spindle following loss of Sirt1 was associated with the deregulation of Plk1 activity. Thus, we conclude that Sirt1 may contribute to a mitotic regulator that controls spindle dynamics through Plk1 activity, resulting in fine-tuning of Plk1 dependent microtubule dynamics.
College of Natural Sciences, Department of Life Sciences, Sogang University, Seoul, 121-742, Republic of Korea.
Jin-Ju
JJ
Kim
College of Natural Sciences, Department of Life Sciences, Sogang University, Seoul, 121-742, Republic of Korea.
Na-Yeon
NY
Gil
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, Republic of Korea.
Xiang Hua
XH
Zhang
Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, Inchoen, Republic of Korea.
Kwang-Hoon
KH
Chun
Genentech, Inc., South San Francisco, California, 94080.
Guowei
G
Fang
Laboratory of Biochemistry, School of Life Sciences & Biotechnology, Korea University, Seoul, 136-701, Republic of Korea.
Joon
J
Kim
Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea.
Hyeseong
H
Cho
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, Republic of Korea.
Chang-Young
CY
Jang
College of Natural Sciences, Department of Life Sciences, Sogang University, Seoul, 121-742, Republic of Korea.
Hyuk-Jin
HJ
Cha
D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D056564:Sirtuin 1; D000097869:Polo-Like Kinase 1; C447939:SIRT1 protein, human
MICROTUBULE DYNAMICS; MITOTIC ARREST; NOCODAZOLE; Plk1; Sirt1