Association with cullin partners protects ROC proteins from proteasome-dependent degradation

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Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
05:35

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins

Published on: March 3, 2016

T Ohta1, J J Michel, Y Xiong

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill 27599-7295, USA.

Oncogene
|December 22, 1999
PubMed

Insights

ROC1 and ROC2 proteins are essential for ubiquitin ligase activity. Their stability and function depend on association with cullins, suggesting a novel regulatory mechanism for E3 ligases.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Cullin 1/CDC53 proteins are involved in ubiquitin-mediated proteolysis.
  • ROC1 and ROC2 are related RING finger proteins similar to APC11.
  • ROC1 is a crucial component of CUL1 and CDC53 ubiquitin ligases.

Purpose of the Study:

  • To investigate the regulation and function of ROC1, ROC2, and APC11.
  • To understand the role of cullin association in ROC protein stability and ligase activity.

Main Methods:

  • Gene expression analysis of ROC1, ROC2, and APC11.
  • Analysis of ectopically expressed ROC proteins stability.
  • Site-directed mutagenesis of ROC1 RING finger residues.
  • Assessment of ubiquitin ligase activity.

Main Results:

  • ROC1, ROC2, and APC11 gene expression is induced by mitogens and cell cycle-constant.
  • Ectopically expressed ROC proteins are proteasome-degraded but stabilized by cullin association.
  • Mutations in ROC1's RING finger impair cullin binding, stability, and ligase activity.

Conclusions:

  • ROC-cullin ligase activity is regulated by complex assembly and ROC/APC11 ubiquitination.
  • Cullin association is critical for protecting ROC proteins from degradation and maintaining ligase function.

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