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Signaling disrupts mSin3A binding to the Mad1‐like Sin3‐interacting domain of TIEG2, an Sp1‐like repressor
Author(s) -
Ellenrieder Volker,
Zhang JinSan,
Kaczynski Joanna,
Urrutia Raul
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.10.2451
Subject(s) - biology , repressor , genetics , microbiology and biotechnology , dna binding protein , transcription factor , gene
A Sin3‐interacting domain (SID) originally described in Mad proteins is necessary for both transcriptional repression and growth suppression by these transcription factors. We recently reported that a structurally and functionally related Mad1‐like SID is also present in five Sp1‐like repressor proteins (TIEG1, TIEG2, BTEB1, BTEB3 and BTEB4), demonstrating that SID–mSin3A interactions have a wider functional impact on transcriptional repression. SID–mSin3A interaction is necessary for the anti‐proliferative function of Mad, TIEG and BTEB proteins. It remains to be established, however, whether the SID–mSin3A interaction is constitutive or regulated. Here, we describe that the Mad1‐like SID domain of the Sp1‐like repressor TIEG2 is inhibited by the epidermal growth factor (EGF)–Ras–MEK1–ERK2 signaling pathway, via phosphorylation of four serine/threonine sites adjacent to the SID. This phenomenon disrupts the SID–mSin3A interaction and thereby inhibits TIEG2's repression activity. Thus, these results show for the first time that the repression of a SID‐containing protein is regulated by signaling rather than functioning in a constitutive manner, extending our understanding of how the function of SID‐containing repressors may be controlled.