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TBP is differentially regulated by c-Jun N-terminal kinase 1 (JNK1) and JNK2 through Elk-1, controlling c-Jun

Shuping Zhong1, Jody Fromm, Deborah L Johnson

  • 1Department of Biochemistry and Molecular Biology, University of Southern California, 2011 Zonal Ave., Los Angeles, CA 90033, USA.

Molecular and Cellular Biology
|November 1, 2006
PubMed

Insights

The c-Jun N-terminal kinases (JNKs), specifically JNK1 and JNK2, differentially regulate TATA-binding protein (TBP) expression. These distinct JNK functions are crucial for controlling cell proliferation.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • The c-Jun N-terminal kinases (JNKs) are a family of stress-activated protein kinases.
  • JNK1 and JNK2 are ubiquitously expressed and have known overlapping functions.
  • The regulation of the TATA-binding protein (TBP), a key transcription factor, is not fully understood in relation to JNK signaling.

Purpose of the Study:

  • To investigate the distinct roles of JNK1 and JNK2 in regulating TBP gene expression.
  • To elucidate the molecular mechanisms by which JNKs control TBP transcription.
  • To determine the impact of JNK-mediated TBP regulation on cellular processes like proliferation.

Main Methods:

  • Gene knockout (Jnk1(-/-) and Jnk2(-/-)) in mouse fibroblasts.
  • RNA interference (siRNA) to reduce JNK1 and JNK2 expression in human hepatoma cells.
  • Analysis of TBP mRNA and protein levels.
  • Investigation of Elk-1 phosphorylation and its binding to the TBP promoter using techniques like Western blotting and chromatin immunoprecipitation.

Main Results:

  • JNK1 deficiency led to decreased TBP expression, while JNK2 deficiency resulted in increased TBP expression in fibroblasts.
  • Similar opposing effects on TBP expression were observed in human hepatoma cells upon reduction of JNK1 versus JNK2.
  • JNKs regulate TBP transcription via phosphorylation of Elk-1, which affects its binding to the TBP promoter.
  • Altered TBP expression by JNKs influenced c-Jun expression and fibroblast proliferation rates.

Conclusions:

  • JNK1 and JNK2 exhibit distinct, non-redundant functions in the transcriptional regulation of TBP.
  • The differential regulation of Elk-1 phosphorylation by JNK1 and JNK2 mediates these opposing effects on TBP expression.
  • These findings reveal novel mechanisms by which JNK signaling pathways control gene expression and cellular proliferation.

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