MLL and CREB bind cooperatively to the nuclear coactivator CREB-binding protein

P. Ernst, J. Wang, M. Huang, Richard Goodman, S. J. Korsmeyer

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

A fragment of the mixed-lineage leukemia (MLL) gene (Mll, HRX, ALL-1) was identified in a yeast genetic screen designed to isolate proteins that interact with the CREB-CREB-binding protein (CBP) complex. When tested for binding to CREB or CBP individually, this MLL fragment interacted directly with CBP, but not with CREB. In vitro binding experiments refined the minimal region of interaction to amino acids 2829 to 2883 of MLL, a potent transcriptional activation domain, and amino acids 581 to 687 of CBP (the CREB-binding or KIX domain). The transactivation activity of MLL was dependent on CBP, as either adenovirus E1A expression, which inhibits CBP activity, or alteration of MLL residues important for CBP interaction proved effective at inhibiting MLL-mediated transactivation. Single amino acid substitutions within the MLL activation domain revealed that five hydrophobic residues, potentially forming a hydrophobic face of an amphipathic helix, were critical for the interaction of MLL with CBP. Using purified components, we found that the MLL activation domain facilitated the binding of CBP to phosphorylated CREB. In contrast with paradigms in which factors compete for limiting quantities of CBP, these results reveal that two distinct transcription factor activation domains can cooperatively target the same motif on CBP.

Original languageEnglish (US)
Pages (from-to)2249-2258
Number of pages10
JournalMolecular and Cellular Biology
Volume21
Issue number7
DOIs
StatePublished - 2001
Externally publishedYes

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CREB-Binding Protein
Leukemia
Transcriptional Activation
Aminoacylation
Amino Acid Substitution
Protein Binding
Adenoviridae
Transcription Factors

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

MLL and CREB bind cooperatively to the nuclear coactivator CREB-binding protein. / Ernst, P.; Wang, J.; Huang, M.; Goodman, Richard; Korsmeyer, S. J.

In: Molecular and Cellular Biology, Vol. 21, No. 7, 2001, p. 2249-2258.

Research output: Contribution to journalArticle

Ernst, P. ; Wang, J. ; Huang, M. ; Goodman, Richard ; Korsmeyer, S. J. / MLL and CREB bind cooperatively to the nuclear coactivator CREB-binding protein. In: Molecular and Cellular Biology. 2001 ; Vol. 21, No. 7. pp. 2249-2258.
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