Identification of domains of c-Jun mediating androgen receptor transactivation

S C Wise1, L A Burmeister, X F Zhou

  • 1University of Toledo, Department of Biology, Ohio 43606, USA.

Oncogene
|May 20, 1998
PubMed

Insights

The proto-oncoprotein c-Jun indirectly stimulates androgen receptor transactivation via its activation functions, independent of its DNA-binding ability. This study identifies key c-Jun domains essential for this distinct regulatory mechanism.

Area of Science:

  • Molecular Biology
  • Oncogenesis
  • Gene Regulation

Background:

  • The proto-oncoprotein c-Jun, as part of the AP-1 complex, regulates gene transcription via DNA binding.
  • Previously, an indirect mechanism of c-Jun regulating transcription by stimulating androgen receptor (AR) transactivation was reported, independent of c-Fos or DNA binding.

Purpose of the Study:

  • To characterize the specific domains of c-Jun responsible for stimulating androgen receptor transactivation.
  • To investigate the role of c-Jun's transactivation ability in this indirect mechanism.

Main Methods:

  • Utilized a series of c-Jun mutants to identify critical domains.
  • Employed c-Jun/v-Jun chimeras to assess functional differences.
  • Analyzed c-Jun's effect on androgen receptor-mediated transactivation using a transactivation-deficient mutant.

Main Results:

  • A functional basic leucine zipper (bZIP) region and N-terminal activation functions of c-Jun are necessary for stimulating AR transactivation.
  • v-Jun cannot stimulate AR transactivation, highlighting the importance of c-Jun's specific activation functions.
  • c-Jun exhibits bell-shaped activity on AR transactivation, distinct from its own transactivation capacity.
  • A c-Jun mutant lacking transactivation ability can still stimulate AR activity.

Conclusions:

  • c-Jun's ability to stimulate androgen receptor transactivation is separable from its intrinsic transactivation function.
  • The N-terminal activation functions of c-Jun are crucial for its indirect regulation of AR.
  • This finding reveals a novel, DNA-binding-independent regulatory role for c-Jun in androgen receptor signaling.

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