Interaction of PP2A catalytic subunit with Rb2/p130 is required for all‐trans retinoic acid suppression of ovarian carcinoma cell growth
- 4 October 2005
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 206 (2), 495-502
- https://doi.org/10.1002/jcp.20490
Abstract
All‐trans retinoic acid (ATRA) treatment causes CAOV3 ovarian carcinoma cells to growth arrest in the G0/G1 phase and to elevate the level of Rb2/p130 protein. PP2A, a serine/threonine phosphatase, binds and dephosphorylates Rb2/p130, thereby increasing the half‐life of Rb2/p130 in the cell. In order to further characterize the interaction between Rb2/p130 and PP2A upon ATRA treatment, we examined the posttranslational modification of PP2A. ATRA treatment leads to hypophosphorylation of PP2A catalytic subunit (PP2Ac) that correlates with increased PP2A activity. In addition, the N‐terminus of PP2Ac binds directly to NLS sequences located in the C‐terminus of Rb2/p130. Furthermore, CAOV3 cells transfected with a truncated Rb2/p130 construct consisting of only the wt C‐terminus grew more aggressively and were less sensitive to ATRA treatment when compared to parental CAOV3 cells. In contrast, CAOV3 cells transfected with a truncated Rb2/p130 construct consisting of only the C‐terminus in which the NLS sites were mutated and which could not interact with PP2A, were as sensitive to ATRA treatment as parental CAOV3 cells. These studies suggest that ATRA treatment suppresses the growth of CAOV3 cells via a novel posttranscriptional mechanism involving PP2A. J. Cell. Physiol. 206: 495–502, 2006.Keywords
This publication has 51 references indexed in Scilit:
- Specific interactions of PP2A and PP2A-like phosphatases with the yeast PTPA homologues, Ypa1 and Ypa2Biochemical Journal, 2005
- PP2A Phosphatase Activity Is Required for Stress and Tor Kinase Regulation of Yeast Stress Response Factor Msn2pEukaryotic Cell, 2004
- Frequent Loss of pRb2/p130 in Human Ovarian CarcinomaClinical Cancer Research, 2004
- Modulation of Thr Phosphorylation of Integrin β1 during Muscle DifferentiationPublished by Elsevier BV ,2004
- Elucidation of Molecular Events Mediating Induction of Apoptosis by Synthetic Retinoids Using a CD437-resistant Ovarian Carcinoma Cell LinePublished by Elsevier BV ,2002
- Protein Phosphatase 2A Holoenzyme AssemblyJournal of Biological Chemistry, 2002
- Nucleocytoplasmic Shuttling of p130/RBL2: Novel Regulatory MechanismMolecular and Cellular Biology, 2002
- Functional interaction between a novel protein phosphatase 2A regulatory subunit, PR59, and the retinoblastoma-related p107 proteinOncogene, 1999
- Reduction of both RAR and RXR Levels Is Required to Maximally Alter Sensitivity of CA-OV3 Ovarian Tumor Cells to Growth Suppression by all-trans-Retinoic AcidExperimental Cell Research, 1997
- 13-cis-Retinoic Acid in the Treatment of Oral LeukoplakiaNew England Journal of Medicine, 1986