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

Volker Ellenrieder, Jin S. Zhang, Joanna Kaczynski, Raul Urrutia

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2451-2460
Number of pages10
JournalEMBO Journal
Volume21
Issue number10
DOIs
StatePublished - May 15 2002

Fingerprint

Repressor Proteins
Threonine
Epidermal Growth Factor
Serine
Phosphorylation
Proteins
Transcription Factors
Growth
Protein Domains

Keywords

  • EGF
  • mSin3A
  • Repression
  • SID
  • TIEG2

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of TIEG2, an Sp1-like repressor. / Ellenrieder, Volker; Zhang, Jin S.; Kaczynski, Joanna; Urrutia, Raul.

In: EMBO Journal, Vol. 21, No. 10, 15.05.2002, p. 2451-2460.

Research output: Contribution to journalArticle

Ellenrieder, Volker ; Zhang, Jin S. ; Kaczynski, Joanna ; Urrutia, Raul. / Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of TIEG2, an Sp1-like repressor. In: EMBO Journal. 2002 ; Vol. 21, No. 10. pp. 2451-2460.
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