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. 2002 Mar 15;277(11):8999-9009.
doi: 10.1074/jbc.M110453200. Epub 2002 Jan 4.

Covalent attachment of the SUMO-1 protein to the negative regulatory domain of the c-Myb transcription factor modifies its stability and transactivation capacity

Juraj Bies  1 , Ján Markus, Linda Wolff
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Free article

Covalent attachment of the SUMO-1 protein to the negative regulatory domain of the c-Myb transcription factor modifies its stability and transactivation capacity

Juraj Bies et al. J Biol Chem. .
Free article

Abstract

The transcription factor c-Myb is subject to several types of post-translational modifications, including phosphorylation, acetylation, and ubiquitination. These modifications regulate the transcription and transforming activity as well as the proteolytic stability of c-Myb. Here we report the covalent modification of c-Myb with the small ubiquitin-related protein SUMO-1. Mutational analysis identified two major sumolation sites (Lys(499) and Lys(523)) in the negative regulatory domain. Interestingly, the single mutation K523R completely abolished modification of c-Myb with SUMO-1, suggesting that sumolation of Lys(523) is required for modification of other lysines in c-Myb. In accordance with this observation, we found that the SUMO-1-conjugating enzyme Ubc9 interacted only with a region surrounding Lys(523) (also called the PEST/EVES motif). Experiments aimed at determining the proteolytic stability of sumolated and unmodified forms of c-Myb revealed that at least two covalently attached SUMO-1 molecules dramatically increased the stability of c-Myb. However, mutations of the SUMO-1 modification sites did not alter its stability, suggesting that a mechanism(s) other than competition of ubiquitin and SUMO-1 for the same lysine is involved in the stabilization of sumolated c-Myb protein. Finally, the K523R mutant of c-Myb, entirely deficient in sumolation, was shown to have an increased transactivation capacity on a Myb-responsive promoter, suggesting that SUMO-1 negatively regulates the transactivation function of c-Myb. Thus, modification of c-Myb with SUMO-1 represents a novel mechanism through which the negative regulatory domain can exert its suppressing activity on c-Myb transactivation capacity.

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