TY - JOUR
T1 - TRE-dependent transcription activation by JDP2-CHOP10 association
AU - Weidenfeld-baranboim, Keren
AU - Bitton-worms, Keren
AU - Aronheim, Ami
N1 - Funding Information:
The authors wish to thank Drs David Ron, Ariel Stanhill, Silvio J. Gutkind, Tsonwin Hai, Richard G. Pestell and Adi Salzberg for various reagents, Drs Edith Suss-Toby and Offer Shenker, Ms. Aviva Cohen and Mr. Yaakov Sakoury for technical help. This work was initiated thanks to the students participated in the 2005 protein interaction course at the faculty of Medicine of the Technion. This Research was partially funded by the Israel Cancer Association through the donation from the ICA friends in Switzerland and by the Israel Cancer Research Foundation RCDA grant to A.A. Funding to pay the Open Access publication charges for this article was provided by the Rappaport Family Institute for Research in the Medical Sciences.
PY - 2008/6
Y1 - 2008/6
N2 - The c-Jun dimerization protein 2, JDP2, is a member of the activating protein 1 (AP-1) family of transcription factors. Overexpression of JDP2 has been shown to result in repression of AP-1-dependent transcription and inhibition of cellular transformation. Other studies suggested that JDP2 may function as an oncogene. Here we describe the identification of CHOP10, a member of the CCAAT enhancer binding proteins, as a protein associating with JDP2. In contrast to the inhibition of transcription by JDP2, JDP2-CHOP complex strongly enhances transcription from promoters containing TPA response elements (TRE), but not from those containing cyclic AMP response elements (CRE). The association between JDP2 and CHOP10 involves the leucine zipper motifs of both proteins, whereas, the basic domain of CHOP10 contributes to the association of the JDP2-CHOP10 complex with the DNA. DNA binding of JDP2-CHOP complex is observed both in vitro and in vivo. Finally, overexpression of JDP2 results in increased cell viability following ER stress and counteracts CHOP10 pro-apoptotic activity. JDP2 expression may determine the threshold for cell sensitivity to ER stress. This is the first report describing TRE-dependent activation of transcription by JDP2 and thus may provide an explanation for the as yet unexplored oncogenic properties of JDP2.
AB - The c-Jun dimerization protein 2, JDP2, is a member of the activating protein 1 (AP-1) family of transcription factors. Overexpression of JDP2 has been shown to result in repression of AP-1-dependent transcription and inhibition of cellular transformation. Other studies suggested that JDP2 may function as an oncogene. Here we describe the identification of CHOP10, a member of the CCAAT enhancer binding proteins, as a protein associating with JDP2. In contrast to the inhibition of transcription by JDP2, JDP2-CHOP complex strongly enhances transcription from promoters containing TPA response elements (TRE), but not from those containing cyclic AMP response elements (CRE). The association between JDP2 and CHOP10 involves the leucine zipper motifs of both proteins, whereas, the basic domain of CHOP10 contributes to the association of the JDP2-CHOP10 complex with the DNA. DNA binding of JDP2-CHOP complex is observed both in vitro and in vivo. Finally, overexpression of JDP2 results in increased cell viability following ER stress and counteracts CHOP10 pro-apoptotic activity. JDP2 expression may determine the threshold for cell sensitivity to ER stress. This is the first report describing TRE-dependent activation of transcription by JDP2 and thus may provide an explanation for the as yet unexplored oncogenic properties of JDP2.
UR - http://www.scopus.com/inward/record.url?scp=46349099090&partnerID=8YFLogxK
U2 - 10.1093/nar/gkn268
DO - 10.1093/nar/gkn268
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AN - SCOPUS:46349099090
SN - 0305-1048
VL - 36
SP - 3608
EP - 3619
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 11
ER -
