Abstract
The ATM-related TRRAP protein is a component of several different histone acetyltransferase (HAT) complexes but lacks the kinase activity characteristic of other ATM family members. We identified a novel function for this evolutionarily conserved domain in its requirement for the assembly of a functional HAT complex. Ectopic expression of TRRAP protein with a mutation in the ATM-related domain inhibits Myc-mediated oncogenic transformation. The Myc-binding region of TRRAP maps to a separable domain, and ectopic expression of this domain inhibits cell growth. These findings demonstrate that the ATM-related domain of TRRAP forms a structural core for the assembly and recruitment of HAT complexes by transcriptional activators.
MeSH Terms
Acetylation
Acetyltransferases/metabolism
Adaptor Proteins, Signal Transducing
Animals
Ataxia Telangiectasia Mutated Proteins
Binding Sites
Carrier Proteins/metabolism
Cell Cycle Proteins
Cell Line
Cell Transformation, Neoplastic
DNA-Binding Proteins
Histone Acetyltransferases
Histones/metabolism
Humans
Nuclear Proteins/genetics,metabolism
Protein Serine-Threonine Kinases/metabolism
Proto-Oncogene Proteins c-myc/genetics,metabolism
Rats
Recombinant Fusion Proteins/genetics,metabolism
Saccharomyces cerevisiae Proteins
Trans-Activators/metabolism
Transcription Factors
Tumor Suppressor Proteins
p300-CBP Transcription Factors
Chemicals
Adaptor Proteins, Signal Transducing
Carrier Proteins
Cell Cycle Proteins
DNA-Binding Proteins
Histones
Nuclear Proteins
Proto-Oncogene Proteins c-myc
Recombinant Fusion Proteins
SUPT3H protein, human
Saccharomyces cerevisiae Proteins
Trans-Activators
Transcription Factors
Tumor Suppressor Proteins
transformation-transcription domain-associated protein
Acetyltransferases
Histone Acetyltransferases
p300-CBP Transcription Factors
p300-CBP-associated factor
ATM protein, human
Ataxia Telangiectasia Mutated Proteins
Protein Serine-Threonine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Park J
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544-1014, USA.
Kunjibettu S
McMahon S B
Cole M D
References (20)
20 references, click to expand
-
Acetylation of histones and transcription-related factors.
Microbiol Mol Biol Rev. 2000 Jun;64(2):435-59
PMID: 10839822
-
Three yeast proteins related to the human candidate tumor suppressor p33(ING1) are associated with histone acetyltransferase activities.
Mol Cell Biol. 2000 Jun;20(11):3807-16
PMID: 10805724
-
PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints.
Science. 1995 Oct 6;270(5233):50-1
PMID: 7569949
-
Transformation of primary rat embryo cells.
Methods Enzymol. 1995;254:37-41
PMID: 8531699
-
A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A.
Nature. 1996 Jul 25;382(6589):319-24
PMID: 8684459
-
Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines.
Nature. 1996 Sep 19;383(6597):269-72
PMID: 8805705
-
The transcriptional coactivators p300 and CBP are histone acetyltransferases.
Cell. 1996 Nov 29;87(5):953-9
PMID: 8945521
-
Histone acetyltransferase activity is conserved between yeast and human GCN5 and is required for complementation of growth and transcriptional activation.
Mol Cell Biol. 1997 Jan;17(1):519-27
PMID: 8972232
-
Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex.
Genes Dev. 1997 Jul 1;11(13):1640-50
PMID: 9224714
-
The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins.
Cell. 1998 Aug 7;94(3):363-74
PMID: 9708738
-
Tra1p is a component of the yeast Ada.Spt transcriptional regulatory complexes.
J Biol Chem. 1998 Oct 9;273(41):26559-65
PMID: 9756893
-
The ATM-related cofactor Tra1 is a component of the purified SAGA complex.
Mol Cell. 1998 Dec;2(6):863-7
PMID: 9885573
-
The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily.
Mol Cell. 1998 Dec;2(6):869-75
PMID: 9885574
-
Identification of TATA-binding protein-free TAFII-containing complex subunits suggests a role in nucleosome acetylation and signal transduction.
J Biol Chem. 1999 Jun 25;274(26):18285-9
PMID: 10373431
-
Requirement of sequences outside the conserved kinase domain of fission yeast Rad3p for checkpoint control.
Mol Biol Cell. 1999 Oct;10(10):3223-38
PMID: 10512862
-
The Spt components of SAGA facilitate TBP binding to a promoter at a post-activator-binding step in vivo.
Genes Dev. 1999 Nov 15;13(22):2940-5
PMID: 10580001
-
The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc.
Mol Cell Biol. 2000 Jan;20(2):556-62
PMID: 10611234
-
Inhibition of TATA-binding protein function by SAGA subunits Spt3 and Spt8 at Gcn4-activated promoters.
Mol Cell Biol. 2000 Jan;20(2):634-47
PMID: 10611242
-
FAT: a novel domain in PIK-related kinases.
Trends Biochem Sci. 2000 May;25(5):225-7
PMID: 10782091
-
An ATPase/helicase complex is an essential cofactor for oncogenic transformation by c-Myc.
Mol Cell. 2000 Feb;5(2):321-30
PMID: 10882073