The P300/CBP-associated Factor (PCAF) is a Cofactor of ATF4 for Amino Acid-regulated Transcription of CHOP

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2007 Aug 30

PMID 17726049

Citations 39

Authors

Yoan Cherasse

Anne-Catherine Maurin

Cedric Chaveroux

Celine Jousse

Valerie Carraro

Laurent Parry

Christiane Deval

Christophe Chambon

Pierre Fafournoux

Alain Bruhat

Affiliations

Soon will be listed here.

Abstract

When an essential amino acid is limited, a signaling cascade is triggered that leads to increased translation of the 'master regulator', activating transcription factor 4 (ATF4), and resulting in the induction of specific target genes. Binding of ATF4 to the amino acid response element (AARE) is an essential step in the transcriptional activation of CHOP (a CCAAT/enhancer-binding protein-related gene) by amino acid deprivation. We set out to identify proteins that interact with ATF4 and that play a role in the transcriptional activation of CHOP. Using a tandem affinity purification (TAP) tag approach, we identified p300/CBP-associated factor (PCAF) as a novel interaction partner of ATF4 in leucine-starved cells. We show that the N-terminal region of ATF4 is required for a direct interaction with PCAF and demonstrate that PCAF is involved in the full transcriptional response of CHOP by amino acid starvation. Chromatin immunoprecipitation analysis revealed that PCAF is engaged on the CHOP AARE in response to amino acid starvation and that ATF4 is essential for its recruitment. We also show that PCAF stimulates ATF4-driven transcription via its histone acetyltransferase domain. Thus PCAF acts as a coactivator of ATF4 and is involved in the enhancement of CHOP transcription following amino acid starvation.

Citing Articles

Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells.

Yang L, Qi C, Lu S, Ye X, Merikhian P, Zhang D Nat Commun. 2025; 16(1):524.

PMID: 39789010 PMC: 11718104. DOI: 10.1038/s41467-024-55738-1.

Spatial Transcriptomic Study Reveals Heterogeneous Metabolic Adaptation and a Role of Pericentral PPARα/CAR/Ces2a Axis During Fasting in Mouse Liver.

Wang S, Xu B, Liang J, Feng Y, Han P, Shen J Adv Sci (Weinh). 2024; 11(41):e2405240.

PMID: 39234807 PMC: 11538668. DOI: 10.1002/advs.202405240.

A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response.

Neill G, Masson G Front Mol Neurosci. 2023; 16:1112253.

PMID: 36825279 PMC: 9941348. DOI: 10.3389/fnmol.2023.1112253.

GCN4 Enhances the Transcriptional Regulation of AreA by Interacting with SKO1 To Mediate Nitrogen Utilization in Ganoderma lucidum.

Lian L, Shi L, Zhu J, Shi L, Ren A, You H Appl Environ Microbiol. 2022; 88(22):e0132222.

PMID: 36342130 PMC: 9680636. DOI: 10.1128/aem.01322-22.

The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer.

Ghaddar N, Wang S, Woodvine B, Krishnamoorthy J, van Hoef V, Darini C Nat Commun. 2021; 12(1):4651.

PMID: 34330898 PMC: 8324901. DOI: 10.1038/s41467-021-24661-0.

References

Jin Y, Zeng S, Lee H, Lu H . MDM2 mediates p300/CREB-binding protein-associated factor ubiquitination and degradation. J Biol Chem. 2004; 279(19):20035-43. DOI: 10.1074/jbc.M309916200. View

Lassot I, Estrabaud E, Emiliani S, Benkirane M, Benarous R, Margottin-Goguet F . p300 modulates ATF4 stability and transcriptional activity independently of its acetyltransferase domain. J Biol Chem. 2005; 280(50):41537-45. DOI: 10.1074/jbc.M505294200. View

Puri P, Sartorelli V, Yang X, Hamamori Y, Ogryzko V, Howard B . Differential roles of p300 and PCAF acetyltransferases in muscle differentiation. Mol Cell. 1998; 1(1):35-45. DOI: 10.1016/s1097-2765(00)80005-2. View

Gachon F, Thebault S, Peleraux A, Devaux C, Mesnard J . Molecular interactions involved in the transactivation of the human T-cell leukemia virus type 1 promoter mediated by Tax and CREB-2 (ATF-4). Mol Cell Biol. 2000; 20(10):3470-81. PMC: 85640. DOI: 10.1128/MCB.20.10.3470-3481.2000. View

Sartorelli V, Puri P, Hamamori Y, Ogryzko V, Chung G, Nakatani Y . Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program. Mol Cell. 2000; 4(5):725-34. DOI: 10.1016/s1097-2765(00)80383-4. View

De Angelis R, Iezzi S, Bruno T, Corbi N, Di Padova M, Floridi A . Functional interaction of the subunit 3 of RNA polymerase II (RPB3) with transcription factor-4 (ATF4). FEBS Lett. 2003; 547(1-3):15-9. DOI: 10.1016/s0014-5793(03)00659-8. View

Bruhat A, Jousse C, Carraro V, Reimold A, Ferrara M, Fafournoux P . Amino acids control mammalian gene transcription: activating transcription factor 2 is essential for the amino acid responsiveness of the CHOP promoter. Mol Cell Biol. 2000; 20(19):7192-204. PMC: 86273. DOI: 10.1128/MCB.20.19.7192-7204.2000. View

Gachon F, Gaudray G, Thebault S, Basbous J, Koffi J, Devaux C . The cAMP response element binding protein-2 (CREB-2) can interact with the C/EBP-homologous protein (CHOP). FEBS Lett. 2001; 502(1-2):57-62. DOI: 10.1016/s0014-5793(01)02646-1. View

Gachon F, Devaux C, Mesnard J . Activation of HTLV-I transcription in the presence of Tax is independent of the acetylation of CREB-2 (ATF-4). Virology. 2002; 299(2):271-8. DOI: 10.1006/viro.2002.1501. View

10.

Madison D, Yaciuk P, Kwok R, Lundblad J . Acetylation of the adenovirus-transforming protein E1A determines nuclear localization by disrupting association with importin-alpha. J Biol Chem. 2002; 277(41):38755-63. DOI: 10.1074/jbc.M207512200. View

11.

Harding H, Zhang Y, Zeng H, Novoa I, Lu P, Calfon M . An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell. 2003; 11(3):619-33. DOI: 10.1016/s1097-2765(03)00105-9. View

12.

Sano Y, Tokitou F, Dai P, Maekawa T, Yamamoto T, Ishii S . CBP alleviates the intramolecular inhibition of ATF-2 function. J Biol Chem. 1998; 273(44):29098-105. DOI: 10.1074/jbc.273.44.29098. View

13.

Tontonoz P, Hu E, Spiegelman B . Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994; 79(7):1147-56. DOI: 10.1016/0092-8674(94)90006-x. View

14.

Siu F, Bain P, Chen H, Kilberg M . ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene. J Biol Chem. 2002; 277(27):24120-7. DOI: 10.1074/jbc.M201959200. View

15.

Rigaut G, Shevchenko A, Rutz B, Wilm M, Mann M, Seraphin B . A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol. 1999; 17(10):1030-2. DOI: 10.1038/13732. View

16.

Harding H, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M . Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell. 2000; 6(5):1099-108. DOI: 10.1016/s1097-2765(00)00108-8. View

17.

Kimball S, Jefferson L . Amino acids as regulators of gene expression. Nutr Metab (Lond). 2004; 1(1):3. PMC: 524028. DOI: 10.1186/1743-7075-1-3. View

18.

Martinez-Balbas M, Bauer U, Nielsen S, Brehm A, Kouzarides T . Regulation of E2F1 activity by acetylation. EMBO J. 2000; 19(4):662-71. PMC: 305604. DOI: 10.1093/emboj/19.4.662. View

19.

Vinson C, Hai T, Boyd S . Dimerization specificity of the leucine zipper-containing bZIP motif on DNA binding: prediction and rational design. Genes Dev. 1993; 7(6):1047-58. DOI: 10.1101/gad.7.6.1047. View

20.

Sylvester S, ap Rhys C, Holbrook N . Induction of GADD153, a CCAAT/enhancer-binding protein (C/EBP)-related gene, during the acute phase response in rats. Evidence for the involvement of C/EBPs in regulating its expression. J Biol Chem. 1994; 269(31):20119-25. View