PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation.
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 Plk1, during prophase, and (2) cleavage of centromeric cohesin by separase at the metaphase-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 Plk1 by RNA interference (RNAi) restores centromeric localization of Sgo1 and prevents chromosome missegregation in cells depleted of PP2A_Aalpha. Our findings suggest that Bub1 targets PP2A to centromeres, which in turn maintains Sgo1 at centromeres by counteracting Plk1-mediated chromosome removal of Sgo1.
Tang
Zhanyun
Z
Department of Pharmacology, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390, USA.
Shu
Hongjun
H
Qi
Wei
W
Mahmood
Nadir A
NA
Mumby
Marc C
MC
Yu
Hongtao
H
D018797:Cell Cycle Proteins / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism*; D020090:Chromosome Segregation; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000378:metabolism; D034622:RNA Interference; D014407:Tumor Cells, Cultured; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C496644:SGO1 protein, human; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein