The tumor supressor PP2A A regulates the RalA GTPase (Cell, 2007, 129:969-982)

報告日期: 2007/11/09
報告時間: 16:00/16:50
報告學生: 郭怡孜
講評老師: 蔣輯武

The Tumor Suppressor PP2A Ab Regulates the RalA GTPase


Anna A. Sablina, Wen Chen, Jason D. Arroyo, Laura Corral, Melissa Hector, Sara E. Bulmer, James A. DeCaprio, and William C. Hahn


Cell, 2007, 129:969-982


Speaker : Yi-Zih Kuo (郭怡孜)

Commentator : Chi-Wu Chiang (蔣輯武老師)

Date : 2007/11/9 16:00-16:50

Room : 602



Reversible protein phosphorylation plays a critical role in cell physiology, and phosphorylation dysregulation contributes directly to disease. Several serine-threonine protein phosphatase 2A (PP2A) heterotrimeric complexes have been implicated in cancer development. Recent studies have shown that somatic mutations in the PP2A Ab structural subunit occur in many human tumors, suggesting that this subunit participates in malignant transformation. However, the mechanism of PP2A Ab mutations contributes to cell transformation remain undefined. In this study, authors used a short hairpin RNA specific for knocking down Ab (shAb) in immortal, nontumorigenic HEK cells expressing large T antigen (LT), telomerase catalytic subunit (hTERT), and H-Ras to investigate the role of PP2A Ab in cell transformation. The results showed that suppression of PP2A Ab expression contributed directly to cell transformation and loss-of-function of both Ab alleles was necessary to induce a fully transformed phenotype. In addition, this study also found that wild-type PP2A Ab but not cancer-derived Ab mutants form a complex with the small GTPase RalA. Moreover, PP2A Ab dephosphorylate RalA at Ser183 and Ser194 and suppression of PP2A Ab led to cellular transformation induced by RalA activation. These observations identify PP2A Ab as a tumor suppressor gene that transforms immortalized human cells by regulating the function of RalA.



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