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Updated: Jun 29, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Dual roles for coactivator activator and its counterbalancing isoform coactivator modulator in human kidney cell

Yun Kyoung Kang1, Rachel Schiff, Lan Ko

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

Cancer Research
|October 3, 2008
PubMed

Insights

Coactivator activator (CoAA) acts as a tumor suppressor in kidney cancer by inhibiting cell growth and down-regulating the c-myc oncogene. A related isoform, CoAM, counterbalances this effect.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Coactivator activator (CoAA) is known to regulate transcription and RNA splicing.
  • Its role in cancer, particularly kidney cancer, is not well understood.

Purpose of the Study:

  • To investigate the function of CoAA as a coregulator in human kidney cells.
  • To determine CoAA's role in renal cell carcinoma (RCC).

Main Methods:

  • Assessed CoAA's effect on cell cycle progression (G1-S transition) and anchorage-independent growth.
  • Analyzed the regulation of c-myc, ccnd1, skp2, and p27/Kip1 protein levels.
  • Investigated CoAA's mechanism of c-myc repression involving HDAC3, histone acetylation, and RNA polymerase II recruitment.
  • Examined the function of the CoAA splicing isoform, coactivator modulator (CoAM).
  • Compared CoAA protein expression in normal kidney tissue versus RCC.

Main Results:

  • CoAA inhibits G1-S transition, anchorage-independent growth, and xenograft tumor formation.
  • CoAA down-regulates c-myc, ccnd1, and skp2, leading to p27/Kip1 accumulation.
  • CoAA represses c-myc by recruiting HDAC3, reducing histone H3 acetylation and RNA polymerase II at the c-myc promoter.
  • The CoAM isoform antagonizes CoAA's inhibitory effects.
  • CoAA protein expression is significantly decreased in human RCC compared to normal kidney tissue.

Conclusions:

  • CoAA functions as a dual-role coregulator, inhibiting cell cycle progression and tumor growth.
  • CoAA acts as a tumor suppressor in renal carcinoma by repressing the proto-oncogene c-myc.
  • CoAM serves as a counterbalancing splice isoform.
  • CoAA represents a novel nuclear receptor coregulator involved in kidney cancer suppression, highlighting potential new roles for coregulators in RCC biology.

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