Characterization of overexpression of the alternatively spliced isoform of the protein phosphatase 2A catalytic subunit in cells

  • Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):491-498. doi: 10.1016/j.bbrc.2017.10.093.
Shen Tang  1 ,  Yuyang Liu  2 ,  Xinhang Wang  3 ,  Ziwei Liang  3 ,  Haiqing Cai  3 ,  Laiming Mo  1 ,  Deqiang Xiao  4 ,  Songchao Guo  4 ,  Yiqiang Ouyang  4 ,  Bin Sun  3 ,  Cailing Lu  5 ,  Xiyi Li  6
Affiliations
  • 1. School of Preclinical medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.
  • 2. Hunan Provincial Center for Disease Control and Prevention, Changsha, Hunan, 410005, China.
  • 3. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, China; School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China.
  • 4. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, China.
  • 5. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, China; School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China. Electronic address: [email protected].
  • 6. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, China; School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China. Electronic address: [email protected].
PMID: 29066346 DOI: 10.1016/j.bbrc.2017.10.093
Abstract

PP2Acα2 is a recently discovered PP2Acα alternative splicing isoform that can be induced following serum withdrawal. It shows enhanced binding to immunoglobulin binding protein 1 and is overexpressed in Chronic Lymphocytic Leukemia patients. Current knowledge concerning PP2Acα2 is limited. In this study, we induced and cloned PP2Acα2 from HL-60 cells and human lymphocytes, transfected them into human embryonic kidney 293 cells and constructed a stable overexpression cell line. We found that PP2Acα2 mRNA inhibits expression of its longer isoform PP2Acα mRNA but had no effect on the final protein expression and modification of this longer isoform. Moreover, PP2Acα2-overexpressed cells demonstrated increased expression of IGBP1, activated mTORC1 signaling to reduce basal Autophagy and increased anchorage-independent growth. Our study provides new insights into the complex mechanisms of PP2A regulation.

Keywords
Anchorage-independent growth; Autophagy; Protein phosphatase 2A; Splicing isoform; mTORC1.