Cancerous inhibitor of protein phosphatase 2A promotes premature chromosome segregation and aneuploidy in prostate cancer cells through association with shugoshin.
Yeast two-hybrid (Y2H) studies have shown that cancerous Inhibitor of protein phosphatase 2A (CIP2A) interacted with several proteins, including leucine-rich repeat-containing protein 59 (LRRC59), suggesting that CIP2A may interact with the chromosome maintenance protein, shugoshin (Sgol1). We previously showed that LRRC59 interacted with CIP2A, which was required for CIP2A nuclear localization. Thus, we predicted that CIP2A and Sgol1 may also interact. Sgol1 is a nuclear protein that regulates chromosome segregation during cell division via protection of cohesin ring proteins. Here, we demonstrated that Sgol1 and the C-terminus of CIP2A interact in prostate carcinoma cell lines in a protein phosphatase 2A (PP2A)-dependent manner. Moreover, we demonstrated that depletion of CIP2A in PC-3 cells decreases premature chromosome segregation, whereas overexpression of CIP2A in an immortalized prostate cell line increases premature chromosome segregation. Importantly, we further showed that CIP2A depletion decreases the incidence of aneuploidy and stabilizes cohesin complex proteins, while overexpression of CIP2A destabilizes Sgol1. Thus, our findings strongly suggest that CIP2A promotes cell cycle progression, premature chromosome segregation, and aneuploidy, possibly through a novel interaction with Sgol1.
Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, Genesis Biotechnology Group, LLC, 1000 Waterview Drive, Hamilton, NJ, 08691, USA.
Rajash
R
Pallai
Aishwarya
A
Bhaskar
Natalie
N
Barnett-Bernodat
Christina
C
Gallo-Ebert
Joseph T
JT
Nickels
Lyndi M
LM
Rice
D000782:Aneuploidy; D017209:Apoptosis / Q000235:genetics; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D020090:Chromosome Segregation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011485:Protein Binding
D001324:Autoantigens; C500266:CIP2A protein, human; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C574205:LRRC59 protein, human; D008565:Membrane Proteins; C496644:SGO1 protein, human