TBP is differentially regulated by c-Jun N-terminal kinase 1 (JNK1) and JNK2 through Elk-1, controlling c-Jun expression and cell proliferation.
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.
Zhong
Shuping
S
Department of Biochemistry and Molecular Biology, University of Southern California, 2011 Zonal Ave., Los Angeles, CA 90033, USA.
Fromm
Jody
J
Johnson
Deborah L
DL
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology*; D048056:Mitogen-Activated Protein Kinase 9 / Q000502:physiology*; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D035181:TATA-Box Binding Protein / Q000096:biosynthesis* / Q000502:physiology*; D014158:Transcription, Genetic; D050807:ets-Domain Protein Elk-1 / Q000502:physiology*
D050784:Proto-Oncogene Protein c-ets-1; D016755:Proto-Oncogene Proteins c-jun; D035181:TATA-Box Binding Protein; D050807:ets-Domain Protein Elk-1; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8