p300 and CBP: Partners for life and death

p300 and CBP are highly related nuclear proteins, which have been implicated in transcriptional responses to disparate extracellular and intracellular signals. There are at least two very good reasons for which p300 and CBP have attracted the attention of the scientific world. First, they belong to an unique class of transcription co‐activators possessing histone acetyltransferase activity and therefore have the potential to reveal basic aspects pertaining to regulation of chromatin structure. Second, p300 and CBP deliver essential functions in virtually all known cellular programs, including the decision to grow, to differentiate, or to commit suicide by apoptosis. Consistent with the complexity of these processes, a multitude of intracellular factors physically interact with p300 and CBP. Thus, the task of many investigations has been the understanding of how these proteins receive signals in the cells, what induces their recruitment in a given signal transduction pathway, and what determines the final outcome of their individual activity. This review will focus on mechanistic and theoretical questions pertaining to the mode of action of p300 and CBP posed by works performed in animal and in vitro model systems. J. Cell. Physiol. 181:218–230, 1999. © 1999 Wiley‐Liss, Inc.

[1]  T. Jacks,et al.  A subset of p53-deficient embryos exhibit exencephaly , 1995, Nature Genetics.

[2]  G. Condorelli,et al.  Human p300 Protein Is a Coactivator for the Transcription Factor MyoD (*) , 1996, The Journal of Biological Chemistry.

[3]  T. Iwama,et al.  p300 gene alterations in colorectal and gastric carcinomas. , 1996, Oncogene.

[4]  Wen‐Ming Yang,et al.  Histone Deacetylases Associated with the mSin3 Corepressor Mediate Mad Transcriptional Repression , 1997, Cell.

[5]  K. Sakaguchi,et al.  DNA damage activates p53 through a phosphorylation-acetylation cascade. , 1998, Genes & development.

[6]  Thorsten Heinzel,et al.  A CBP Integrator Complex Mediates Transcriptional Activation and AP-1 Inhibition by Nuclear Receptors , 1996, Cell.

[7]  L. Kedes,et al.  Regulation of Histone Acetyltransferases p300 and PCAF by the bHLH Protein Twist and Adenoviral Oncoprotein E1A , 1999, Cell.

[8]  M. Carey,et al.  The Enhanceosome and Transcriptional Synergy , 1998, Cell.

[9]  M. Rivera,et al.  A Role for CREB Binding Protein and p300 Transcriptional Coactivators in Ets-1 Transactivation Functions , 1998, Molecular and Cellular Biology.

[10]  A. Lassar,et al.  Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1-dependent kinase , 1995, Science.

[11]  Guillermina Lozano,et al.  Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53 , 1995, Nature.

[12]  C. Allis,et al.  Steroid receptor coactivator-1 is a histone acetyltransferase , 1997, Nature.

[13]  J. Darnell,et al.  Two contact regions between Stat1 and CBP/p300 in interferon γ signaling , 1996 .

[14]  G. Nabel,et al.  Modulation of cytokine‐induced HIV gene expression by competitive binding of transcription factors to the coactivator p300 , 1998, The EMBO journal.

[15]  S. Tapscott,et al.  Functional antagonism between c-Jun and MyoD proteins: A direct physical association , 1992, Cell.

[16]  Y. Hayashi,et al.  Adenoviral E1A-associated protein p300 is involved in acute myeloid leukemia with t(11;22)(q23;q13). , 1997, Blood.

[17]  C. Allis,et al.  Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo. , 1998, Genes & development.

[18]  B. Howard,et al.  The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases , 1996, Cell.

[19]  D. Livingston,et al.  A family of transcriptional adaptor proteins targeted by the E1A oncoprotein , 1995, Nature.

[20]  R. Evans,et al.  Nuclear Receptor Coactivator ACTR Is a Novel Histone Acetyltransferase and Forms a Multimeric Activation Complex with P/CAF and CBP/p300 , 1997, Cell.

[21]  Andrew J. Bannister,et al.  The CBP co-activator is a histone acetyltransferase , 1996, Nature.

[22]  S. Berger,et al.  Histone acetyltransferase activity is conserved between yeast and human GCN5 and is required for complementation of growth and transcriptional activation , 1997, Molecular and cellular biology.

[23]  Tae Hoon Kim,et al.  Efficient recruitment of TFIIB and CBP-RNA polymerase II holoenzyme by an interferon-beta enhanceosome in vitro. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Livingston,et al.  Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation. , 1996, Genes & development.

[25]  Jun Qin,et al.  Histone-like TAFs within the PCAF Histone Acetylase Complex , 1998, Cell.

[26]  P. Chambon,et al.  Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants. , 1994, Development.

[27]  R. Maione,et al.  Interdependence between muscle differentiation and cell-cycle control. , 1997, Biochimica et biophysica acta.

[28]  L. Poellinger,et al.  Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of theCBP/p300 coactivator by the hypoxia‐induciblefactor‐1α , 1998, The EMBO journal.

[29]  N. Shikama,et al.  Functional interplay between p53 and E2F through co-activator p300 , 1998, Oncogene.

[30]  D. Livingston,et al.  Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation , 1998, Nature.

[31]  C. Prives.  Signaling to p53 Breaking the MDM2–p53 Circuit , 1998, Cell.

[32]  S. Ishii,et al.  Drosophila CBP is required for dorsal–dependent twist gene expression , 1997, Nature Genetics.

[33]  S. Horinouchi,et al.  Trichostatin A and trapoxin: Novel chemical probes for the role of histone acetylation in chromatin structure and function , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[34]  N. Shiama.  The p300/CBP family: integrating signals with transcription factors and chromatin. , 1997, Trends in cell biology.

[35]  E. White,et al.  p300 binding by E1A cosegregates with p53 induction but is dispensable for apoptosis , 1997, Journal of virology.

[36]  R. Evans,et al.  A Viral Mechanism for Inhibition of p300 and PCAF Acetyltransferase Activity , 1999, Cell.

[37]  A. Giordano,et al.  Roles of p300, pocket proteins, and hTBP in E1A‐mediated transcriptional regulation and inhibition of p53 transactivation activity , 1997, Journal of cellular biochemistry.

[38]  N. Jones,et al.  p300 and ATF-2 are components of the DRF complex, which regulates retinoic acid- and E1A-mediated transcription of the c-jun gene in F9 cells. , 1998, Genes & development.

[39]  J. Girault,et al.  Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A , 1998, Nature.

[40]  M. Yaffe,et al.  Analysis of an activator:coactivator complex reveals an essential role for secondary structure in transcriptional activation. , 1998, Molecular cell.

[41]  S. Berger,et al.  p53 Sites Acetylated In Vitro by PCAF and p300 Are Acetylated In Vivo in Response to DNA Damage , 1999, Molecular and Cellular Biology.

[42]  S. Bhattacharya,et al.  Cooperation of Stat2 and p300/CBP in signalling induced by interferon-α , 1996, Nature.

[43]  C. Disteche,et al.  The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB–binding protein , 1996, Nature Genetics.

[44]  C. Prives,et al.  p53: puzzle and paradigm. , 1996, Genes & development.

[45]  F. Gage,et al.  The Signal-Dependent Coactivator CBP Is a Nuclear Target for pp90RSK , 1996, Cell.

[46]  M. Merika,et al.  Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription. , 1998, Molecular cell.

[47]  D. Livingston,et al.  p300 family members associate with the carboxyl terminus of simian virus 40 large tumor antigen , 1997, Journal of virology.

[48]  Peter E Wright,et al.  Solution Structure of the KIX Domain of CBP Bound to the Transactivation Domain of CREB: A Model for Activator:Coactivator Interactions , 1997, Cell.

[49]  S. Schreiber,et al.  A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p , 1996, Science.

[50]  L. Kedes,et al.  Differential roles of p300 and PCAF acetyltransferases in muscle differentiation. , 1997, Molecular cell.

[51]  B. Howard,et al.  A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A , 1996, Nature.

[52]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[53]  K. Struhl.  Histone acetylation and transcriptional regulatory mechanisms. , 1998, Genes & development.

[54]  Wei Gu,et al.  Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain , 1997, Cell.

[55]  D. Reinberg,et al.  Histone Deacetylases and SAP18, a Novel Polypeptide, Are Components of a Human Sin3 Complex , 1997, Cell.

[56]  S. Ishii,et al.  CBP as a transcriptional coactivator of c-Myb. , 1996, Genes & development.

[57]  Raoul C. M. Hennekam,et al.  Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP , 1995, Nature.

[58]  S. Berger,et al.  CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein. , 1997, Cancer research.

[59]  L. Magnaghi-Jaulin,et al.  Retinoblastoma protein represses transcription by recruiting a histone deacetylase , 1998, Nature.

[60]  B. Howard,et al.  The SV40 large T antigen and adenovirus E1a oncoproteins interact with distinct isoforms of the transcriptional co‐activator, p300. , 1996, The EMBO journal.

[61]  B. Turner,et al.  Essential and redundant functions of histone acetylation revealed by mutation of target lysines and loss of the Gcn5p acetyltransferase , 1998, The EMBO journal.

[62]  Wei Gu,et al.  Synergistic activation of transcription by CBP and p53 , 1997, Nature.

[63]  R. Goodman,et al.  Adenoviral ElA-associated protein p300 as a functional homologue of the transcriptional co-activator CBP , 1995, Nature.

[64]  S. Berger,et al.  Absence of Gcn5 HAT activity defines a novel state in the opening of chromatin at the PHO5 promoter in yeast. , 1998, Molecular cell.

[65]  D. Livingston,et al.  Phosphorylation of the adenovirus E1A‐associated 300 kDa protein in response to retinoic acid and E1A during the differentiation of F9 cells. , 1995, The EMBO journal.

[66]  T. Tsukiyama,et al.  Chromatin remodeling and transcription. , 1997, Current opinion in genetics & development.

[67]  A. Nordheim,et al.  MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP. , 1996, Biochemical and biophysical research communications.

[68]  Andrew J. Bannister,et al.  Stimulation of c-Jun activity by CBP: c-Jun residues Ser63/73 are required for CBP induced stimulation in vivo and CBP binding in vitro. , 1995, Oncogene.

[69]  M. Breuning,et al.  Conjunction dysfunction: CBP/p300 in human disease. , 1998, Trends in genetics : TIG.

[70]  Andrew J. Bannister,et al.  CBP‐induced stimulation of c‐Fos activity is abrogated by E1A. , 1995, The EMBO journal.

[71]  D. Housman,et al.  MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3). , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[72]  A. Wolffe,et al.  Acetylation of general transcription factors by histone acetyltransferases , 1997, Current Biology.

[73]  L. Donehower,et al.  Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours , 1992, Nature.

[74]  M. Karin,et al.  Activation of cAMP and mitogen responsive genes relies on a common nuclear factor , 1994, Nature.

[75]  D. Lane,et al.  Regulation of the specific DNA binding function of p53 , 1992, Cell.

[76]  Ralf Janknecht,et al.  Transcriptional control: Versatile molecular glue , 1996, Current Biology.

[77]  T. Hunter,et al.  TGF-beta-stimulated cooperation of smad proteins with the coactivators CBP/p300. , 1998, Genes & development.

[78]  C. Allis,et al.  Special HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation. , 1996, Current opinion in genetics & development.

[79]  M. Oren,et al.  p53 in growth control and neoplasia. , 1996, Biochimica et biophysica acta.

[80]  D. Dean,et al.  Rb Interacts with Histone Deacetylase to Repress Transcription , 1998, Cell.

[81]  R. Derynck,et al.  The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation. , 1998, Genes & development.

[82]  Yoichi Taya,et al.  DNA Damage-Induced Phosphorylation of p53 Alleviates Inhibition by MDM2 , 1997, Cell.

[83]  M. Montminy,et al.  Adaptor-mediated Recruitment of RNA Polymerase II to a Signal-dependent Activator (*) , 1996, The Journal of Biological Chemistry.

[84]  C. Glass,et al.  Transcription factor-specific requirements for coactivators and their acetyltransferase functions. , 1998, Science.

[85]  P. Yaciuk,et al.  Analysis with specific polyclonal antiserum indicates that the E1A-associated 300-kDa product is a stable nuclear phosphoprotein that undergoes cell cycle phase-specific modification , 1991, Molecular and cellular biology.

[86]  R. Eckner.  p300 and CBP as transcriptional regulators and targets of oncogenic events. , 1996, Biological chemistry.

[87]  H. Masuya,et al.  Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndrome. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[88]  G. Nabel,et al.  Regulation of NF-κB by Cyclin-Dependent Kinases Associated with the p300 Coactivator , 1997, Science.

[89]  D. Lane,et al.  MDM2--arbiter of p53's destruction. , 1997, Trends in biochemical sciences.

[90]  D. Livingston,et al.  Binding and modulation of p53 by p300/CBP coactivators , 1997, Nature.

[91]  C. Glass,et al.  Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[92]  Alan P. Wolffe,et al.  Targeting Chromatin Disruption: Transcription Regulators that Acetylate Histones , 1996, Cell.

[93]  K. Gardner,et al.  Recruitment of p300/CBP in p53-Dependent Signal Pathways , 1997, Cell.

[94]  David Newsome,et al.  Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300 , 1998, Cell.

[95]  E. Harlow,et al.  Cellular targets for transformation by the adenovirus E1A proteins , 1989, Cell.

[96]  A. Giordano,et al.  p300 is required for MyoD‐dependent cell cycle arrest and muscle‐specific gene transcription , 1997, The EMBO journal.

[97]  M. Yoshida,et al.  Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. , 1993, The Journal of biological chemistry.

[98]  Andrew J. Bannister,et al.  The TAFII250 Subunit of TFIID Has Histone Acetyltransferase Activity , 1996, Cell.

[99]  Jeffrey D. Parvin,et al.  RNA Helicase A Mediates Association of CBP with RNA Polymerase II , 1997, Cell.

[100]  W. El-Deiry,et al.  Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region , 1997, Oncogene.

[101]  J B Lawrence,et al.  Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. , 1994, Genes & development.

[102]  Lawrence A. Donehower,et al.  Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53 , 1995, Nature.

[103]  S. Bhattacharya,et al.  An essential role for p300/CBP in the cellular response to hypoxia. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[104]  E. White,et al.  Suppression of the p300-dependent mdm2 negative-feedback loop induces the p53 apoptotic function. , 1998, Genes & development.

[105]  Xing Shen,et al.  TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein. , 1998, Molecular biology of the cell.

[106]  D. Livingston,et al.  p300/MDM2 complexes participate in MDM2-mediated p53 degradation. , 1998, Molecular cell.

[107]  S. Berger,et al.  Identification of human proteins functionally conserved with the yeast putative adaptors ADA2 and GCN5 , 1996, Molecular and cellular biology.

[108]  A. Berns,et al.  Requirement for a functional Rb-1 gene in murine development , 1992, Nature.

[109]  V. Ogryzko,et al.  Regulation of activity of the transcription factor GATA-1 by acetylation , 1998, Nature.

[110]  Michael R. Green,et al.  Nuclear protein CBP is a coactivator for the transcription factor CREB , 1994, Nature.

[111]  Tony Kouzarides,et al.  Retinoblastoma protein recruits histone deacetylase to repress transcription , 1998, Nature.

[112]  F. Kashanchi,et al.  Phosphorylation of p53 Serine 15 Increases Interaction with CBP* , 1998, The Journal of Biological Chemistry.