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Quantitative Comparison of cis-Regulatory Element (CRE) Activities in Transgenic Drosophila melanogaster
08:19

Quantitative Comparison of cis-Regulatory Element (CRE) Activities in Transgenic Drosophila melanogaster

Published on: December 19, 2011

Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of

S K Lee1, S Y Jung, Y S Kim

  • 1Center for Ligand and Transcription, Department of Biology, Chonnam National University, Kwangju 500-757, Korea.

Molecular Endocrinology (Baltimore, Md.)
|February 7, 2001
PubMed

Insights

ASC-2, a cancer-amplified transcriptional coactivator, binds nuclear receptors and recruits CBP. This interaction is crucial for nuclear receptor-mediated transactivation, highlighting ASC-2

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • ASC-2 is a transcriptional coactivator amplified in human cancers.
  • It enhances transcription by various factors including nuclear receptors, AP-1, and NFkappaB.
  • ASC-2 possesses two nuclear receptor-interaction domains with critical LXXLL motifs.

Purpose of the Study:

  • To elucidate the mechanism by which ASC-2 interacts with nuclear receptors and mediates transactivation.
  • To identify the specific domains and interactions involved in ASC-2's function.
  • To investigate the role of CBP in ASC-2-mediated nuclear receptor activity.

Main Methods:

  • Analysis of ASC-2's nuclear receptor-binding domains (LXXLL motifs).
  • Construction and testing of dominant negative mutants of ASC-2.
  • Identification and characterization of the autonomous transactivation domain (AD) of ASC-2.
  • Investigating the interaction of ASC-2 with CBP and the effect of E1A.

Main Results:

  • ASC-2 contains two LXXLL motifs, with the C-terminal motif binding LXR and the N-terminal binding multiple nuclear receptors.
  • Subregions of ASC-2 containing these motifs function as dominant negative mutants.
  • The autonomous transactivation domain (AD) of ASC-2 comprises AD1, AD2, and AD3, with AD2 and AD3 binding CBP.
  • CBP-neutralizing E1A and overexpressed AD2 inhibit ASC-2's transactivation function.

Conclusions:

  • ASC-2 directly binds nuclear receptors through its LXXLL motifs.
  • ASC-2 recruits CBP via its AD2 and AD3 domains to mediate nuclear receptor transactivation.
  • These findings clarify the molecular mechanism of ASC-2 in regulating gene expression.

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