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A post-translational modification cascade employing HDAC9-PIASy-RNF4 axis regulates chondrocyte hypertrophy by

Hye-Jeong Choi1, Seongran Kwon1, Dae-Won Kim1

  • 1Department of Biochemistry, Yonsei University, Seoul, Republic of Korea.

Cellular Signalling
|June 18, 2016
PubMed

Insights

The study reveals how Nkx3.2 protein stability is controlled by acetylation and de-acetylation, impacting chondrocyte survival and skeletal development. This involves a novel post-translational modification pathway.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Biochemistry

Background:

  • Nkx3.2 (also known as Bapx1) is crucial for chondrogenesis, chondrocyte viability, and suppressing hypertrophy.
  • The precise regulatory mechanisms governing Nkx3.2 function remain largely unknown.

Purpose of the Study:

  • To elucidate the post-translational modifications controlling Nkx3.2 protein stability.
  • To investigate the role of acetylation, de-acetylation, sumoylation, and ubiquitination in Nkx3.2 regulation.
  • To link these regulatory mechanisms to chondrocyte biology during skeletal development.

Main Methods:

  • Investigated the effects of p300 (acetylation) and HDAC9 (de-acetylation) on Nkx3.2.
  • Analyzed the interplay between HDAC9, PIASy (sumoylation), and RNF4 (ubiquitination) in Nkx3.2 modification.
  • Assessed the impact of these modifications on chondrocyte survival and hypertrophic maturation.

Main Results:

  • p300-induced acetylation and HDAC9-induced de-acetylation critically control Nkx3.2 protein stability.
  • HDAC9-dependent de-acetylation initiates PIASy-mediated sumoylation and RNF4-mediated SUMO-targeted ubiquitination.
  • Nkx3.2 regulation via the HDAC9-PIASy-RNF4 axis influences chondrocyte survival and hypertrophic maturation.

Conclusions:

  • A novel mechanism for controlling protein stability through acetylation, de-acetylation, sumoylation, and ubiquitination is revealed.
  • The HDAC9-PIASy-RNF4 axis plays a significant role in Nkx3.2 post-translational modification.
  • This regulatory pathway is essential for chondrocyte viability and hypertrophic maturation during vertebrate skeletal development.
Keywords:
Acetylation-dependent sumoylationCartilage DevelopmentHDAC9Nkx3.2Sumoylation-dependent ubiquitination

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