Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53

Teufel, Daniel P.; Freund, Stefan; Bycroft, Mark; Fersht, Alan R.

doi:10.1073/pnas.0702010104

Cited by 192 publications

(263 citation statements)

References 53 publications

Supporting

Mentioning

241

Contrasting

Unclassified

Order By: Relevance

“…It has been shown that p53 interacts with the Taz1, Kix, Ibid and Taz2 domains and probably with the IHD domain (Teufel et al, 2007). The strongest binding of unphosphorylated p53 was observed to the Taz2 domain.…”

Section: Introductionmentioning

confidence: 81%

Structure of the Taz2 domain of p300: insights into ligand binding

Miller

Dauter

Cherry³

et al. 2009

Acta Crystallogr D Biol Crystallogr

View full text Add to dashboard Cite

CBP and its paralog p300 are histone acetyl transferases that regulate gene expression by interacting with multiple transcription factors via specialized domains. The structure of a segment of human p300 protein (residues 1723-1836) corresponding to the extended zinc-binding Taz2 domain has been investigated. The crystal structure was solved by the SAD approach utilizing the anomalous diffraction signal of the bound Zn ions. The structure comprises an atypical helical bundle stabilized by three Zn ions and closely resembles the solution structures determined previously for shorter peptides. Residues 1813-1834 from the current construct form a helical extension of the C-terminal helix and make extensive crystalcontact interactions with the peptide-binding site of Taz2, providing additional insights into the mechanism of the recognition of diverse transactivation domains (TADs) by Taz2. On the basis of these results and molecular modeling, a hypothetical model of the binding of phosphorylated p53 TAD1 to Taz2 has been proposed.

show abstract

Section: Introductionmentioning

confidence: 81%

Structure of the Taz2 domain of p300: insights into ligand binding

Miller

Dauter

Cherry³

et al. 2009

Acta Crystallogr D Biol Crystallogr

View full text Add to dashboard Cite

show abstract

“…It clearly consisted of two separate subdomains that may be defined as TAD1 from residues 10-31 and TAD2 from residues 46-67, unlike p53, where TAD1 and TAD2 correspond to residues 1-40 and 41-60, respectively (11). There is a linker between TAD1 and TAD2, broadly corresponding to Q33-G45.…”

Section: Resultsmentioning

confidence: 99%

Molecular basis of the interactions between the p73 N terminus and p300: Effects on transactivation and modulation by phosphorylation

Burge

Teufel²,

Townsley³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The transcription factor p73 belongs to the p53 family of proteins and can transactivate a number of target genes in common with p53. Here, we characterized the interaction of the p73 N terminus with four domains of the transcriptional coactivator p300 and with the negative regulator Mdm2 by using biophysical and cellular measurements. We found that, like p53, the N terminus of p73 contained two distinct transactivation subdomains, comprising residues 10 -30 and residues 46 -67. The p73 N terminus bound weakly to the Taz1, Kix, and IBiD domains of p300 but with submicromolar affinity for Taz2, in contrast to previous reports. We found weaker binding of the p73 N terminus to the p300 domains in vitro correlated with a significant decrease in transactivation activity in a cell line for the QS and T14A mutants, and tighter binding of the phosphomimetic T14D in vitro correlated with an increase in vivo. Further, we found that phosphorylation of T14 increased the affinity of the p73 N terminus for Taz2 10-fold. The phosphomimetic p73␣ T14D caused increased levels of transactivation.

show abstract

“…The site of interaction between the KIX domain and both p53-TADs corresponds with the annotated 9aaTADs and the TAF9 binding site (NMR data, eight out of nine annotated amino acids). Despite the unrecognizable sequence similarity (Table 2 and 3) 4,7 , both p53-TAD1 and p53-TAD2 share the same docking sites on the KIX domain, which may result from the presence of a common motif in the p53 transactivation domains, the 9aaTAD 8 . p53 and further well characterized 9aaTAD-transcription factors, which interact with CBP-p300 and other general co-activator GCN5 are listed in Table 3.…”

mentioning

confidence: 99%

“…Interestingly, CBP-p300 domains KIX, TAZ1, TAZ2 and IBiD are also able to bind p53-9aaTAD1 4,7 ( Table 2). The site of interaction between the KIX domain and both p53-TADs corresponds with the annotated 9aaTADs and the TAF9 binding site (NMR data, eight out of nine annotated amino acids).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300

Piskáček

2009

Nature Precedings

View full text Add to dashboard Cite

9aaTAD interactions with a general transcriptional co-activator TAF9/TAFII31 were reported (NMR and biochemical data: p53, VP16, HSF1, NF-IL6, NF-B and NFAT) 1 . 9aaTAD interactions with KIX domain of further general transcriptional co-activators MED15/Gal11 and CBP-p300 were recently reported (NMR data available for Oaf1, Pdr1 and p53) 2-6 . Oaf1-9aaTAD and Pdr1-9aaTAD 3 upon binding to KIX domain of Med15/Gal11 (9 resp. 12 amino acid long peptides including 9aaTAD) reveal structural similarity, although none of the nine amino acids is conserved in both 9aaTADs (Table 1).The interaction between TAF9 and p53-TAD1 was restricted by NMR to five amino acids (FSDLW) in the first annotated 9aaTAD of p53 (p53-9aaTAD1). The second annotated 9aaTAD (p53-9aaTAD2) and the pseudo-9aaTAD (p53-9aaTADpse) were located in p53-TAD2 (annotated results from 2007 available on www.expasy.ch/tools). Both p53-9aaTAD1 and p53-9aaTAD2 fulfil the criteria of 9aaTAD pattern, amino acid composition and hydrophobic profile (Fig.1).

show abstract

Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53

Cited by 192 publications

References 53 publications

Structure of the Taz2 domain of p300: insights into ligand binding

Structure of the Taz2 domain of p300: insights into ligand binding

Molecular basis of the interactions between the p73 N terminus and p300: Effects on transactivation and modulation by phosphorylation

Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300

Contact Info

Product

Resources

About