RT Journal Article
SR Electronic
T1 Activating Transcription Factor-2 Mediates Transcriptional Regulation of Gluconeogenic Gene PEPCK by Retinoic Acid
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 3400
OP 3407
DO 10.2337/diabetes.51.12.3400
VO 51
IS 12
A1 Lee, Min Young
A1 Jung, Che-Hun
A1 Lee, Keesook
A1 Choi, Yung Hyun
A1 Hong, SunHwa
A1 Cheong, JaeHun
YR 2002
UL http://diabetes.diabetesjournals.org/content/51/12/3400.abstract
AB All-trans-retinoic acid (RA) is known to increase the rate of transcription of the PEPCK gene upon engagement of the RA receptor (RAR). RA also mediates induction of specific gene transcription via several signaling pathways as a nongenomic effect. Here we show that RA upregulation of PEPCK promoter activity requires the cAMP response element (CRE)-1 in addition to the RA-response element and that activating transcription factor-2 (ATF-2) binds the CRE element to mediate this effect. Furthermore, we show that RA treatment potentiates ATF-2-dependent transactivation by inducing specific phosphorylation of ATF-2 by p38β kinase. ATF-2 activation by RA blocked the inhibitory intramolecular interaction of ATF-2 amino and carboxyl terminal domains in a p38β kinase-dependent manner. Consistent with these results, RA treatment increased the DNA binding activity of ATF-2 on the PEPCK CRE-1 sequence. Taken together, the data suggest that RA activates the p38β kinase pathway leading to phosphorylation and activation of ATF-2, thereby enhancing PEPCK gene transcription and glucose production.