STUbL-mediated degradation of the transcription factor MAT?2 requires degradation elements that coincide with corepressor binding sites.
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ABSTRACT: The yeast transcription factor MAT?2 (?2) is a short-lived protein known to be ubiquitylated by two distinct pathways, one involving the ubiquitin-conjugating enzymes (E2s) Ubc6 and Ubc7 and the ubiquitin ligase (E3) Doa10 and the other operating with the E2 Ubc4 and the heterodimeric E3 Slx5/Slx8. Although Slx5/Slx8 is a small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligase (STUbL), it does not require SUMO to target ?2 but instead directly recognizes ?2. Little is known about the ?2 determinants required for its Ubc4- and STUbL-mediated degradation or how these determinants substitute for SUMO in recognition by the STUbL pathway. We describe two distinct degradation elements within ?2, both of which are necessary for ?2 recognition specifically by the Ubc4 pathway. Slx5/Slx8 can directly ubiquitylate a C-terminal fragment of ?2, and mutating one of the degradation elements impairs this ubiquitylation. Surprisingly, both degradation elements identified here overlap specific interaction sites for ?2 corepressors: the Mcm1 interaction site in the central ?2 linker and the Ssn6 (Cyc8) binding site in the ?2 homeodomain. We propose that competitive binding to ?2 by the ubiquitylation machinery and ?2 cofactors is balanced so that ?2 can function in transcription repression yet be short lived enough to allow cell-type switching.
SUBMITTER: Hickey CM
PROVIDER: S-EPMC4591686 | biostudies-literature | 2015 Oct
REPOSITORIES: biostudies-literature
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