AUTOREGULATION OF PROTEIN PHOSPHATASE TYPE 2A EXPRESSION

Protein phosphatases are involved in many cellular processes. One of t he most abundant of these enzymes, the serine/threonine-specific prote in phosphatase type 2A (PP2A), is present in most eukaryotic cells and serves a variety of functions. However, the detailed study of its reg ulation and function has been hampered by the difficulty of manipulati ng its expression level in cell culture. By using a new mammalian expr ession vector to forcibly overexpress PP2A in the mouse fibroblast cel l line NIH3T3, we now show that the catalytic subunit of PP2A is subje ct to a potent autoregulatory mechanism that adjusts PP2A protein to c onstant levels. This control is exerted at the translational level and does not involve regulation of transcription or RNA processing. Thus, our results demonstrate tight control of PP2A expression, and provide an explanation for the difficulty of increasing PP2A expression exper imentally.