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Molecular and Cellular Biology, January 2007, p. 54-64, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.01365-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

TBP Is Differentially Regulated by c-Jun N-Terminal Kinase 1 (JNK1) and JNK2 through Elk-1, Controlling c-Jun Expression and Cell Proliferation{triangledown}

Shuping Zhong, Jody Fromm, and Deborah L. Johnson*

Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, and Norris Comprehensive Cancer Center, 2011 Zonal Ave., Los Angeles, California 90033

Received 25 July 2006/ Returned for modification 24 August 2006/ Accepted 17 October 2006

Emerging evidence supports the idea that the c-Jun N-terminal kinases (JNKs) possess overlapping but distinct functions. The potential roles of the ubiquitously expressed JNK1 and JNK2 in regulating expression of the central transcription initiation factor, TATA-binding protein (TBP), were examined. Relative to wild-type fibroblasts, TBP was decreased in Jnk1–/– cells and increased in Jnk2–/– cells. Similarly, reduction of JNK1 in human hepatoma cells decreased TBP expression, whereas reduction of JNK2 enhanced it. JNK-mediated regulation of TBP expression occurs at the transcriptional level through their ability to target Elk-1, which directly regulates the TBP promoter in response to epidermal growth factor stimulation. JNK1 increases, whereas JNK2 decreases, the phosphorylation state of Elk-1, which differentially affects Elk-1 occupancy at a defined site within the TBP promoter. These JNK-mediated alterations in TBP expression, alone, serve to regulate c-Jun expression and fibroblast proliferation rates. These studies uncovered several new molecular events that distinguish the functions of JNK1 and JNK2 that are critical for their regulation of cellular proliferation.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, University of Southern California, 2011 Zonal Ave., Los Angeles, CA 90033. Phone: (323) 442-1446. Fax: (323) 442-1224. E-mail: johnsond{at}usc.edu.

{triangledown} Published ahead of print on 30 October 2006.

Molecular and Cellular Biology, January 2007, p. 54-64, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.01365-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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