A folding-after-binding mechanism describes the recognition between the transactivation domain of c-Myb and the KIX domain of the CREB-binding protein

2012 ◽  
Vol 428 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Stefano Gianni ◽  
Angela Morrone ◽  
Rajanish Giri ◽  
Maurizio Brunori
Keyword(s):  
Binding Protein ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Binding Mechanism ◽  
Kix Domain

scholarly journals Structural insights into TAZ2 domain–mediated CBP/p300 recruitment by transactivation domain 1 of the lymphopoietic transcription factor E2A

2020 ◽  
Vol 295 (13) ◽  
pp. 4303-4315
Author(s):  
Marina R. Lochhead ◽  
Alexandra D. Brown ◽  
Alyssa C. Kirlin ◽  
Seth Chitayat ◽  
Kim Munro ◽  
...  
Keyword(s):  
B Cell ◽  
Immune Cell ◽  
Binding Protein ◽  
Helical Structure ◽  
Dependent Manner ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Transactivation Domains ◽  
A Cell ◽  
Kix Domain

The E-protein transcription factors guide immune cell differentiation, with E12 and E47 (hereafter called E2A) being essential for B-cell specification and maturation. E2A and the oncogenic chimera E2A-PBX1 contain three transactivation domains (ADs), with AD1 and AD2 having redundant, independent, and cooperative functions in a cell-dependent manner. AD1 and AD2 both mediate their functions by binding to the KIX domain of the histone acetyltransferase paralogues CREB-binding protein (CBP) and E1A-binding protein P300 (p300). This interaction is necessary for B-cell maturation and oncogenesis by E2A-PBX1 and occurs through conserved ΦXXΦΦ motifs (with Φ denoting a hydrophobic amino acid) in AD1 and AD2. However, disruption of this interaction via mutation of the KIX domain in CBP/p300 does not completely abrogate binding of E2A and E2A-PBX1. Here, we determined that E2A-AD1 and E2A-AD2 also interact with the TAZ2 domain of CBP/p300. Characterization of the TAZ2:E2A-AD1(1–37) complex indicated that E2A-AD1 adopts an α-helical structure and uses its ΦXXΦΦ motif to bind TAZ2. Whereas this region overlapped with the KIX recognition region, key KIX-interacting E2A-AD1 residues were exposed, suggesting that E2A-AD1 could simultaneously bind both the KIX and TAZ2 domains. However, we did not detect a ternary complex involving E2A-AD1, KIX, and TAZ2 and found that E2A containing both intact AD1 and AD2 is required to bind to CBP/p300. Our findings highlight the structural plasticity and promiscuity of E2A-AD1 and suggest that E2A binds both the TAZ2 and KIX domains of CBP/p300 through AD1 and AD2.

scholarly journals Nuclear Factor of Activated T Cells (NFAT)-dependent Transactivation Regulated by the Coactivators p300/CREB-binding Protein (CBP)

1998 ◽  
Vol 187 (12) ◽  
pp. 2031-2036 ◽  
Author(s):  
Carmen García-Rodríguez ◽  
Anjana Rao
Keyword(s):  
T Cells ◽  
Binding Protein ◽  
Critical Role ◽  
Regulation Of Transcription ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Activated T Cells ◽  
Viral Oncoprotein

p300 and cAMP response element–binding protein (CREB)–binding protein (CBP) are members of a family of coactivators involved in the regulation of transcription and chromatin. We show that transcription factors of the nuclear factor of activated T cells (NFAT) family bind p300/CBP and recruit histone acetyltransferase activity from T cell nuclear extracts. The NH2-terminal transactivation domain of NFAT1 and the phospho-CREB- and E1A-binding sites of p300/CBP are involved in the interaction. The viral oncoprotein E1A inhibits NFAT-dependent transactivation in a p300-dependent manner. Recruitment of the coactivators p300/CBP by the transactivation domains of NFAT proteins is likely to play a critical role in NFAT-dependent gene expression during the immune response.

scholarly journals Roles of Phosphorylation and Helix Propensity in the Binding of the KIX Domain of CREB-binding Protein by Constitutive (c-Myb) and Inducible (CREB) Activators

2002 ◽  
Vol 277 (44) ◽  
pp. 42241-42248 ◽  
Author(s):  
Tsaffrir Zor ◽  
Bernhard M. Mayr ◽  
H. Jane Dyson ◽  
Marc R. Montminy ◽  
Peter E. Wright
Keyword(s):  
Binding Protein ◽  
Creb Binding Protein ◽  
Helix Propensity ◽  
Kix Domain

scholarly journals Magnitude of the CREB-Dependent Transcriptional Response Is Determined by the Strength of the Interaction between the Kinase-Inducible Domain of CREB and the KIX Domain of CREB-Binding Protein

2000 ◽  
Vol 20 (24) ◽  
pp. 9409-9422 ◽  
Author(s):  
Adam J. Shaywitz ◽  
Simon L. Dove ◽  
Jon M. Kornhauser ◽  
Ann Hochschild ◽  
Michael E. Greenberg
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Protein Interactions ◽  
Mammalian Cells ◽  
Binding Protein ◽  
Full Length ◽  
Mutant Form ◽  
Creb Binding Protein ◽  
Wild Type ◽  
Kix Domain

ABSTRACT The activity of the transcription factor CREB is regulated by extracellular stimuli that result in its phosphorylation at a critical serine residue, Ser133. Phosphorylation of Ser133 is believed to promote CREB-dependent transcription by allowing CREB to interact with the transcriptional coactivator CREB-binding protein (CBP). Previous studies have established that the domain encompassing Ser133 on CREB, known as the kinase-inducible domain (KID), interacts specifically with a short domain in CBP termed the KIX domain and that this interaction depends on the phosphorylation of Ser133. In this study, we adapted a recently described Escherichia coli-based two-hybrid system for the examination of phosphorylation-dependent protein-protein interactions, and we used this system to study the kinase-induced interaction between the KID and the KIX domain. We identified residues of the KID and the KIX domain that are critical for their interaction as well as two pairs of oppositely charged residues that apparently interact at the KID-KIX interface. We then isolated a mutant form of the KIX domain that interacts more tightly with wild-type and mutant forms of the KID than does the wild-type KIX domain. We show that in the context of full-length CBP, the corresponding amino acid substitution resulted in an enhanced ability of CBP to stimulate CREB-dependent transcription in mammalian cells. Conversely, an amino acid substitution in the KIX domain that weakens its interaction with the KID resulted in a decreased ability of full-length CBP to stimulate CREB-dependent transcription. These findings demonstrate that the magnitude of CREB-dependent transcription in mammalian cells depends on the strength of the KID-KIX interaction and suggest that the level of transcription induced by coactivator-dependent transcriptional activators can be specified by the strength of the activator-coactivator interaction.

scholarly journals Site-Specific Acetylation by p300 or CREB Binding Protein Regulates Erythroid Krüppel-Like Factor Transcriptional Activity via Its Interaction with the SWI-SNF Complex

2001 ◽  
Vol 21 (7) ◽  
pp. 2413-2422 ◽  
Author(s):  
Wenjun Zhang ◽  
Shilpa Kadam ◽  
Beverly M. Emerson ◽  
James J. Bieker
Keyword(s):  
Chromatin Structure ◽  
Binding Protein ◽  
Globin Gene ◽  
Critical Role ◽  
Erythroid Cell ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Site Specific ◽  
Acetylation Status

ABSTRACT Recruitment of modifiers and remodelers to specific DNA sites within chromatin plays a critical role in controlling gene expression. The study of globin gene regulation provides a convergence point within which to address these issues in the context of tissue-specific and developmentally regulated expression. In this regard, erythroid Krüppel-like factor (EKLF) is critical. EKLF is a red cell-specific activator whose presence is crucial for establishment of the correct chromatin structure and high-level transcriptional induction of adult β-globin. We now find, by metabolic labeling-immunoprecipitation experiments, that EKLF is acetylated in the erythroid cell. EKLF residues acetylated by CREB binding protein (CBP) in vitro map to Lys-288 in its transactivation domain and Lys-302 in its zinc finger domain. Although site-specific DNA binding by EKLF is unaffected by the acetylation status of either of these lysines, directed mutagenesis of Lys-288 (but not Lys-302) decreases the ability of EKLF to transactivate the β-globin promoter in vivo and renders it unable to be superactivated by coexpressed p300 or CBP. In addition, the acetyltransferase function of CBP or p300 is required for superactivation of wild-type EKLF. Finally, acetylated EKLF has a higher affinity for the SWI-SNF chromatin remodeling complex and is a more potent transcriptional activator of chromatin-assembled templates in vitro. These results demonstrate that the acetylation status of EKLF is critical for its optimal activity and suggest a mechanism by which EKLF acts as an integrator of remodeling and transcriptional components to alter chromatin structure and induce adult β-globin expression within the β-like globin cluster.

scholarly journals Binding of p53 to the KIX Domain of CREB Binding Protein

1999 ◽  
Vol 274 (37) ◽  
pp. 26321-26328 ◽  
Author(s):  
Karen Van Orden ◽  
Holli A. Giebler ◽  
Isabelle Lemasson ◽  
Melissa Gonzales ◽  
Jennifer K. Nyborg
Keyword(s):  
Binding Protein ◽  
Creb Binding Protein ◽  
Kix Domain
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