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Nuclear receptor coactivator/coregulator NCoA6(NRC) is a pleiotropic coregulator involved in transcription, cell

Muktar A Mahajan1, Herbert H Samuels

  • 1Department of Pharmacology, NYU School of Medicine, New York, New York, USA. muktar.mahajan@med.nyu.edu

Nuclear Receptor Signaling
|February 28, 2008
PubMed

Insights

Nuclear receptor coactivator 6 (NCoA6) is essential for gene transcription, embryonic development, and cell survival. Its overexpression in cancers highlights its role in disease and suggests therapeutic potential.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Developmental Biology

Background:

  • Nuclear receptor coactivator 6 (NCoA6), also known as ASC-2, is a multifunctional protein involved in transcriptional regulation.
  • The NCoA6 gene is amplified and overexpressed in various cancers, including breast, colon, and lung cancer.
  • NCoA6 possesses distinct activation domains (AD1, AD2) and regulatory domains (STL) crucial for its function.

Purpose of the Study:

  • To elucidate the multifaceted roles of NCoA6 in transcriptional activation, gene regulation, and cellular processes.
  • To investigate the significance of NCoA6 in embryonic development and its implications in cancer biology.

Main Methods:

  • Analysis of NCoA6 protein structure, including its activation and regulatory domains.
  • Investigation of NCoA6 interactions with nuclear receptors and cofactors like CBP/p300.
  • Utilizing knockout mouse models (NCoA6-/- and conditional knockouts) to study its in vivo functions.

Main Results:

  • NCoA6 acts as a potent coactivator, enhancing transcription of diverse target genes through interactions with nuclear receptors via LxxLL motifs.
  • NCoA6 associates with methyltransferase complexes, suggesting a role in chromatin modulation via histone methylation.
  • NCoA6 knockout embryos exhibit embryonic lethality due to severe growth retardation and developmental defects; NCoA6-/- MEFs show reduced growth and increased apoptosis.

Conclusions:

  • NCoA6 is an essential coactivator indispensable for normal embryonic development, cell growth, and survival.
  • Its role extends to regulating energy homeostasis and wound healing, indicating pleiotropic functions.
  • The overexpression of NCoA6 in cancers underscores its oncogenic potential and suggests it as a therapeutic target.

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