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PMID: 11713276 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

TIP49b, a regulator of activating transcription factor 2 response to stress and DNA damage.

Molecular and cellular biology ·Vol. 21 ·No. 24 ·2001-12-00 ·Pages 8398-413

Cho SG, Bhoumik A, Broday L, Ivanov V, Rosenstein B, Ronai Z

Abstract

Activating transcription factor 2 (ATF2/CRE-BP1) is implicated in transcriptional control of stress-responsive genes. A yeast two-hybrid screen identified TBP-interacting protein 49b (TIP49b), a component of the INO80 chromatin-remodeling complex, as a novel ATF2-interacting protein. TIP49b's association with ATF2 is phosphorylation dependent and requires amino acids 150 to 248 of ATF2 (ATF2(150-248)), which are implicated in intramolecular inhibition of ATF2 transcriptional activities. Forced expression of TIP49b efficiently attenuated ATF2 transcriptional activities under normal growth conditions as well as after UV treatment, ionizing irradiation, or activation of p38 kinase, all of which induced ATF2 phosphorylation and increased TIP49b-ATF2 association. Constitutive expression of ATF2(150-248) peptide outcompeted TIP49b interaction with ATF2 and alleviated the suppression of ATF2 transcriptional activities. Expression of ATF2(150-248) in fibroblasts or melanoma but not in ATF2-null cells caused a profound G(2)M arrest and increased degree of apoptosis following irradiation. The interaction between ATF2 and TIP49b constitutes a novel mechanism that serves to limit ATF2 transcriptional activities and highlights the central role of ATF2 in the control of the cell cycle and apoptosis in response to stress and DNA damage.

MeSH Terms
ATPases Associated with Diverse Cellular Activities Activating Transcription Factor 2 Animals Apoptosis Carrier Proteins/metabolism,physiology Cell Line Cyclic AMP Response Element-Binding Protein/metabolism DNA/metabolism DNA Damage DNA Helicases DNA Repair Fibroblasts/metabolism Flow Cytometry Humans Luciferases/metabolism Mice Mitogen-Activated Protein Kinases/metabolism Phosphorylation Precipitin Tests Protein Binding Protein Structure, Tertiary Retroviridae/genetics Stress, Physiological Time Factors Transcription Factors/metabolism Transcription, Genetic Two-Hybrid System Techniques p38 Mitogen-Activated Protein Kinases
Chemicals
ATF2 protein, human Activating Transcription Factor 2 Atf2 protein, mouse Carrier Proteins Cyclic AMP Response Element-Binding Protein Transcription Factors DNA Luciferases Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases ATPases Associated with Diverse Cellular Activities DNA Helicases RUVBL2 protein, human
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cho S G
The Ruttenberg Cancer Center, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029, USA.
Bhoumik A
Broday L
Ivanov V
Rosenstein B
Ronai Z
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
2001-12-00
Pages
8398-413
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC100004
Subset
IM
Grants
NCI NIH HHS · CA 59905 · United States
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