PHB2 protects sister-chromatid cohesion in mitosis.
Cohesion between sister chromatids is essential for proper chromosome segregation in mitosis. In vertebrate mitotic cells, most cohesin is removed from the chromosome arms [1-4], but centromeric cohesin is protected by shugoshin until the onset of anaphase [5]. However, the mechanism of this protection of centromeric cohesion is not well understood. Here, we demonstrate that prohibitin 2 (PHB2) is involved in the regulation of sister-chromatid cohesion during mitosis in HeLa cells. PHB2 is an evolutionarily conserved protein in eukaryotes and has multiple functions, such as transcriptional regulation and cell viability and development [6-8]. However, its functions in mitosis have not yet been determined. We show that depletion of PHB2 by RNA interference (RNAi) causes premature sister-chromatid separation and defects in chromosome congression accompanied by mitotic arrest by spindle-checkpoint activation. In the absence of PHB2, cohesin is dissociated from centromeres during early mitosis, although the centromeric localization of shugoshin is preserved. Thus, our findings suggest that, in addition to the shugoshin, PHB2 is also required to protect the centromeric cohesion from phosphorylation by Plk1 during early mitosis and that its function is essential for proper mitotic progression.
Takata
Hideaki
H
Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan.
Matsunaga
Sachihiro
S
Morimoto
Akihiro
A
Ma
Nan
N
Kurihara
Daisuke
D
Ono-Maniwa
Rika
R
Nakagawa
Masatoshi
M
Azuma
Takachika
T
Uchiyama
Susumu
S
Fukui
Kiichi
K
D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism; D002503:Centromere / Q000737:chemistry; D002842:Chromatids; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D000091402:Prohibitins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D000091402:Prohibitins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D000097869:Polo-Like Kinase 1; C000717331:PHB2 protein, human; C496644:SGO1 protein, human