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.
Ellenrieder
Volker
V
Gastroenterology Research Unit, Mayo Clinic, Rochester, MN 55905, USA.
Zhang
Jin-San
JS
Kaczynski
Joanna
J
Urrutia
Raul
R
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016384:Consensus Sequence; D006224:Cricetinae; D017930:Genes, Reporter; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D016335:Zinc Fingers
D018797:Cell Cycle Proteins; C486422:Klf13 protein, mouse; D051741:Kruppel-Like Transcription Factors; D011994:Recombinant Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D056264:Sin3 Histone Deacetylase and Corepressor Complex