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 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

scholarly journals Mapping the Promiscuous Binding Interface of HOX-A11 with KIX by Experimentally Guided in-silico docking

2021 ◽  
Author(s):  
Soumya Ganguly ◽  
Günter P. Wagner ◽  
Jens Meiler
Keyword(s):  
Transcription Factor ◽  
Protein Interactions ◽  
Binding Protein ◽  
Creb Binding Protein ◽  
Computational Docking ◽  
In Silico Docking ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Binding Interface ◽  
Kix Domain

AbstractTranscription factors (TFs) regulate levels of transcription through a complex array of protein-protein interactions, thereby controlling key physiological processes such as development, stress response and cell growth. The transcription factor HOXA11 contains an intrinsically disordered regions (IDR) through which it interacts with CREB binding protein (CBP) and regulates endometrial development and function in eutherian mammals. The interaction between the IDR of HOXA11 and CBP was analyzed using computational docking guided by experimental constraints. HOXA11 IDR interacts with the KIX domain of CBP at two discrete sites – MLL and cMyb, mediated by sticky hydrophobic grooves on the surface of KIX. A five residue motif FDQFF on HOXA11 can interact both at cMyb and MLL site of KIX resulting in a promiscuous binding.Author SummaryWe demonstrate how the intrinsically disordered region (IDR) of transcription factor HOXA11 interacts at two distinct sites of the transcription coactivator CREB binding protein (CBP). By combining computational docking with limited experimental data we construct models of the complex of the KIX domain within CBP and a short helical segment within the IDR of HOXA11. The interaction between HOXA11 and CBP is believed to trigger the downstream expression of genes important in embryonic development.

scholarly journals p53 Recruitment of CREB Binding Protein Mediated through Phosphorylated CREB: a Novel Pathway of Tumor Suppressor Regulation

2000 ◽  
Vol 20 (13) ◽  
pp. 4849-4858 ◽  
Author(s):  
Holli A. Giebler ◽  
Isabelle Lemasson ◽  
Jennifer K. Nyborg
Keyword(s):  
Tumor Suppressor ◽  
Transcriptional Activation ◽  
Binding Protein ◽  
Direct Interaction ◽  
Creb Binding Protein ◽  
Creb Phosphorylation ◽  
Cellular Genes ◽  
Kix Domain ◽  
Phosphorylated Creb

ABSTRACT CREB binding protein (CBP) is a 270-kDa nuclear protein required for activated transcription of a large number of cellular genes. Although CBP was originally discovered through its interaction with phosphorylated CREB (pCREB), it is utilized by a multitude of cellular transcription factors and viral oncoproteins. Both CREB and the tumor suppressor p53 have been shown to directly interact with the KIX domain of CBP. Although coactivator competition is an emerging theme in transcriptional regulation, we have made the fortuitous observation that protein kinase A-phosphorylated CREB strongly enhances p53 association with KIX. Phosphorylated CREB also facilitates interaction of a p53 mutant, defective for KIX binding, indicating that CREB functions in a novel way to bridge p53 and the coactivator. This is accomplished through direct interaction between the bZIP domain of CREB and the amino terminus of p53; a protein-protein interaction that is also detected in vivo. Consistent with our biochemical observations, we show that stimulation of the intracellular cyclic AMP (cAMP) pathway, which leads to CREB phosphorylation, strongly enhances both the transcriptional activation and apoptotic properties of p53. We propose that phosphorylated CREB mediates recruitment of CBP to p53-responsive promoters through direct interaction with p53. These observations provide evidence for a novel pathway that integrates cAMP signaling and p53 transcriptional activity.

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 Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein

2019 ◽  
Vol 294 (45) ◽  
pp. 16604-16619 ◽  
Author(s):  
Archit Garg ◽  
Roberto Orru ◽  
Weixiang Ye ◽  
Ute Distler ◽  
Jeremy E. Chojnacki ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Protein ◽  
Creb Binding Protein ◽  
Kix Domain ◽  
Circadian Transcription
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