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

Oncogene volume 18, pages 6758–6766 (1999)Cite this article

Abstract

Cullin 1/CDC53 represents a multigene family and has been linked to the ubiquitin-mediated proteolysis of several different proteins. We recently identified two closely related RING finger proteins, ROC1 and ROC2, that share considerable sequence similarity to an APC subunit, APC11, and demonstrated ROC1 as an essential subunit of CUL1 and CDC53 ubiquitin ligases. We report here that the expression of ROC1, ROC2 and APC11 genes are induced by mitogens and remain constant during the cell cycle. Unlike other subunits of SCF and APC E3 ligases, ectopically expressed ROC family proteins are degraded by a proteasome-inhibitor sensitive pathway and are stabilized by associating with cullins. Mutations at the conserved Phe79 and His80 residues in the RING finger of ROC1 diminish its binding with cullins, resulting in a loss of cullin protection and ubiquitin ligase activity. These results suggest a potential mechanism for regulating the activity of ROC-cullin ligases through complex assembly and ROC/APC11 subunit ubiquitination.

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Acknowledgements

T Ohta is supported in part by the Department of Surgery, St Marianna University School of Medicine. JJ Michel is supported by an US Department of Defense Breast Cancer Research Program pre-doctoral fellowship. Y Xiong is a recipient of American Cancer Society Junior Faculty Award and a Pew Scholar in Biomedical Science. This study was supported by Public Health Service grants CA65572 and CA68377 to Y Xiong.

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Authors and Affiliations

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

    Tomohiko Ohta & Yue Xiong

  2. Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7295, North Carolina, NC, USA

    Jennifer J Michel & Yue Xiong

  3. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7295, North Carolina, NC, USA

    Yue Xiong

  4. Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7295, North Carolina, NC, USA

    Yue Xiong

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  1. Tomohiko Ohta
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Ohta, T., Michel, J. & Xiong, Y. Association with cullin partners protects ROC proteins from proteasome-dependent degradation. Oncogene 18, 6758–6766 (1999). https://doi.org/10.1038/sj.onc.1203115

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