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Roles of SCF and VHL Ubiquitin Ligases in Regulation of Cell Growth

  • Chapter
Protein Degradation in Health and Disease

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 29))

Abstract

Over the past few years, a growing body of evidence has brought to light critical roles for ubiquitin-dependent protein degradation in controlling the cellular levels of a large variety of proteins such as cyclins, cyclin-dependent kinase inhibitors, oncogenes, and tumor suppressors, which play integral roles in regulation of cell growth. Ubiquitin-dependent protein degradation is a complex, multistep process that proceeds with the tagging of target proteins with a poly-ubiquitin chain and culminates with the processive, ubiquitin- dependent degradation of tagged proteins by the 26S proteasome (Hershko et al. 1983; Hochstrasser 1995, 1996; Hershko and Ciechanover 1998). In the first step, the C-terminus of ubiquitin is covalently linked through a thioester bond to the active site cysteine residue of an El ubiquitin-activating enzyme. Ubiquitin is then transferred from the El via a thioester linkage to an active site cysteine residue in one of a number of E2 ubiquitin-conjugating enzymes. Ubiquitin is then either (1) conjugated directly via an isopeptide bond to the 8-amino group of a lysine in the target protein, (2) conjugated via an isopeptide bond to another ubiquitin moiety on the target protein as part of synthesis of the poly-ubiquitin tag, or (3) transferred from the E2 via a thioester bond to an active site cysteine residue in one of a growing family of E3 ubiquitin ligases, which then conjugate ubiquitin to specific target proteins.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Takumi Kamura

  2. Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma, 73104, USA

    Joan W. Conaway & Ronald C. Conaway

  3. Howard Hughes Medical Institute, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma, 73104, USA

    Joan W. Conaway

  4. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, 73190, USA

    Joan W. Conaway

Authors
  1. Takumi Kamura
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  2. Joan W. Conaway
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  3. Ronald C. Conaway
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Editors and Affiliations

  1. Laboratoire d’Enzymologie Moléculaire et Fonctionnelle Département de Biologie Cellulaire Institut Jacques Monod, Universités Paris VI & VII, 2, Place Jussieu, 75251, Paris Cedex 05, France

    Michèle Reboud-Ravaux

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© 2002 Springer-Verlag Berlin Heidelberg

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Kamura, T., Conaway, J.W., Conaway, R.C. (2002). Roles of SCF and VHL Ubiquitin Ligases in Regulation of Cell Growth. In: Reboud-Ravaux, M. (eds) Protein Degradation in Health and Disease. Progress in Molecular and Subcellular Biology, vol 29. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56373-7_1

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  • DOI: https://doi.org/10.1007/978-3-642-56373-7_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62714-9

  • Online ISBN: 978-3-642-56373-7

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