Editors' ChoicePosttranslational modification

p53 Activation by SUMO Addition

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Science's STKE  23 Nov 1999:
Vol. 1999, Issue 9, pp. tw2
DOI: 10.1126/stke.1999.9.tw2

Under normal growth conditions, cells maintain a low concentration of the transcription factor and tumor suppressor protein p53. This occurs through the conjugation of p53 to ubiquitin molecules, a modification that signals its degradation by the ubiquitin-proteosome pathway. Conditions of stress, such as DNA damage, cause an increase in cellular p53 and subsequent activation of p53-dependent events such as the control of cell cycle progression and apoptosis. Two groups report that a ubiquitin-related molecule called the small ubiquitin-related modifier (SUMO) is also conjugated to p53. "Sumolation" was observed in vitro and in vivo. The site of SUMO addition was mapped to a single lysine residue at the COOH-terminus of p53. Mutation of this residue did not inhibit ubiquitination of the protein, although this residue may also be a site of ubiquitin addition. Unlike the addition of multiple ubiquitin molecules to p53, only one molecule of SUMO is appended. Sumolation increased the transcription activity of p53, but it remains to be determined how SUMO activates p53 and whether this modification contributes to the growth suppressing properties of p53.

Rodriguez, M.S., Desterro, J.M.P., Lain, S., Midgley, C.A., Lane, D.P., and Hay, R.T. (1999) SUMO-1 modification activates the transcriptional response of p53. EMBO J. 18: 6455-6451. [Abstract] [Full Text]

Gostissa, M., Hengstermann, A., Fogal, V., Sandy, P., Schwarz, S.E., Scheffner, M., and Del Sal, G. (1999) Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. EMBO J. 18: 6462-6471. [Abstract] [Full Text]

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