TIP49b, a regulator of activating transcription factor 2 response to stress and DNA damage.
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.
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The Ruttenberg Cancer Center, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029, USA.
Bhoumik
A
A
Broday
L
L
Ivanov
V
V
Rosenstein
B
B
Ronai
Z
Z
D000074183:ATPases Associated with Diverse Cellular Activities; D051698:Activating Transcription Factor 2; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000235:genetics; D013312:Stress, Physiological; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D048051:p38 Mitogen-Activated Protein Kinases
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D004247:DNA; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human