PP2A is required for centromeric localization of sgol and proper chromosome segregation

被引：267

作者：

Tang, Zhanyun ^{[1
]}

Shu, Hongjun ^{[1
]}

Qi, Wei ^{[1
]}

Mahmood, Nadir A. ^{[1
]}

Mumby, Marc C. ^{[1
]}

Yu, Hongtao ^{[1
]}

机构：

[1] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA

来源：

DEVELOPMENTAL CELL | 2006年 / 10卷 / 05期

关键词：

D O I：

10.1016/j.devcel.2006.03.010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Loss of sister-chromatid cohesion triggers chromosome segregation in mitosis and occurs through two mechanisms in vertebrate cells: (1) phosphorylation and removal of cohesin from chromosome arms by mitotic kinases, including PIk1, during prophase, and (2) cleavage of centromeric cohesin by separase at the meta phase-anaphase transition. Bub1 and the MEI-S332/Shugoshin (Sgo1) family of proteins protect centromeric cohesin from mitotic kinases during prophase. We show that human Sgo1 binds to protein phosphatase 2A (PP2A). PP2A localizes to centromeres in a Bub1-dependent manner. The Sgo1-PP2A interaction is required for centromeric localization of Sgo1 and proper chromosome segregation in human cells. Depletion of PIk1 by RNA interference (RNAi) restores centromeric localization of Sgo1 and prevents chromosome missegregation in cells depleted of PP2A_A alpha. Our findings suggest that Bub1 targets PP2A to centromeres, which in turn maintains Sgo1 at centromeres by counteracting PIK1-mediated chromosome removal of Sgo1.

引用

页码：575 / 585

页数：11

共 37 条

[21] Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells
McGuinness, BE
Hirota, T
Kudo, NR
Peters, JM
Nasmyth, K
[J]. PLOS BIOLOGY, 2005, 3 (03) : 433 - 449
[22] The spindle checkpoint: Structural insights into dynamic signalling
Musacchio, A
Hardwick, KG
[J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (10) : 731 - 741
[23] Splitting the chromosome: Cutting the ties that bind sister chromatids
Nasmyth, K
Peters, LM
Uhlmann, F
[J]. SCIENCE, 2000, 288 (5470) : 1379 - 1384
[24] Un menage a quatre: The molecular biology of chromosome segregation in meiosis
Petronczki, M
Siomos, MF
Nasmyth, K
[J]. CELL, 2003, 112 (04) : 423 - 440
[25] Two fission yeast homologs of Drosophila Mei-S332 are required for chromosome segregation during meiosis I and II
Rabitsch, KP
Gregan, J
Schleiffer, A
Javerzat, JP
Eisenhaber, F
Nasmyth, K
[J]. CURRENT BIOLOGY, 2004, 14 (04) : 287 - 301
[26] Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis
Salic, A
Waters, JC
Mitchison, TJ
[J]. CELL, 2004, 118 (05) : 567 - 578
[27] Silverstein AM, 2003, METHOD ENZYMOL, V366, P361
[28] Critical role for protein phosphatase 2A heterotrimers in mammalian cell survival
Strack, S
Cribbs, JT
Gomez, L
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (46) : 47732 - 47739
[29] Maintenance of sister-chromatid cohesion at the centromere by the Drosophila MEI-S332 protein
Tang, TTL
Bickel, SE
Young, LM
Orr-Weaver, TL
[J]. GENES & DEVELOPMENT, 1998, 12 (24) : 3843 - 3856
[30] Tang Zhanyun, 2004, Methods Mol Biol, V281, P227

← 1 2 3 4 →