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

摘要

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. Highlights ? PP2Acα2 mRNA inhibits expression of its longer isoform PP2Acα mRNA. ? PP2Acα2 overexpression increases expression of IGBP1. ? PP2Acα2 overexpression activates mTORC1 signaling to reduce basal autophagy. ? PP2Acα2 overexpression increases anchorage-independent growth.