Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of TIEG2, an Sp1-like repressor.

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.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Animals, Binding Sites, CHO Cells, Cell Cycle Proteins, Consensus Sequence, Cricetinae, Genes, Reporter, Kruppel-Like Transcription Factors, Mice, Phosphorylation, Protein Binding, Recombinant Proteins, Repressor Proteins, Signal Transduction, Sp1 Transcription Factor, Transcription Factors, Transfection, Zinc Fingers
EMBO J.
Date: May. 15, 2002
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