Editors' ChoicePost-Translational Modifications

Regulation by Methylation

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Science's STKE  07 Nov 2000:
Vol. 2000, Issue 57, pp. tw3
DOI: 10.1126/stke.2000.57.tw3

Posttranslational modifications are important mechanisms for regulating protein activity. The catalytic subunit (C) of the protein phosphatase PP2A is modified by phosphorylation and carboxyl methylation. The interactions of the C subunit with regulatory B subunits and a scaffold subunit (A) are believed to contribute to the control of target specificity of PP2A. In vitro studies showed that carboxyl methylation of the C subunit influences the interaction of the AC dimer with the B subunit. Wu et al. identified the genes for the yeast carboxyl methyltransferase (PPM1 and PPM2) and the gene for the yeast methylesterase (PPE1) and found that only PPM1 and PPE1 appear to have measurable activity toward PP2A. By using genetic analysis, the consequences of altered levels of methylation of the C subunit on PP2A activity and regulatory protein interactions were studied. Ppm1 mutant yeast exhibit defects similar to those of yeast with defective B subunits, suggesting that methylation may influence the interaction of the C subunit with the B subunits. Furthermore, loss of PPM1 activity resulted in an enhanced interaction with another regulatory partner called Tap42. Thus, if the level of methylation of the C subunit changes in response to stimuli or during the cell cycle, this may help to control the distribution of the C subunit among various regulatory partners and, so, influence the pathway regulated by PP2A at any given time.

Wu, J., Tolstykh, T., Lee, J., Boyd, K., Stock, J.B., and Broach, J.R. (2000) Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivo. EMBO J. 19: 5672-5681. [Abstract] [Full Text]

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