View the Current Issue

Article

  • The EMBO Journal (2003) 22, 1488 - 1496
  • doi:10.1093/emboj/cdg158

Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrate

Mingsheng Zhang1, Cecile M. Pickart2 and Philip Coffino1

  1. Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA
  2. Department of Biochemistry and Molecular Biology, Johns Hopkins University, Baltimore, MD 21205, USA

Correspondence to:

Philip Coffino, E-mail: pcoffin@itsa.ucsf.edu

Received 11 December 2002; Accepted 17 February 2003; Revised 27 January 2003

Ornithine decarboxylase (ODC) is regulated by its metabolic products through a feedback loop that employs a second protein, antizyme 1 (AZ1). AZ1 accelerates the degradation of ODC by the proteasome. We used purified components to study the structural elements required for proteasomal recognition of this ubiquitin-independent substrate. Our results demonstrate that AZ1 acts on ODC to enhance the association of ODC with the proteasome, not the rate of its processing. Substrate-linked or free polyubiquitin chains compete for AZ1-stimulated degradation of ODC. ODC–AZ1 is therefore recognized by the same element(s) in the proteasome that mediate recognition of polyubiquitin chains. The 37 C-terminal amino acids of ODC harbor an AZ1-modulated recognition determinant. Within the ODC C terminus, three subsites are functionally distinguishable. The five terminal amino acids (ARINV, residues 457–461) collaborate with residue C441 to constitute one recognition element, and AZ1 collaborates with additional constituents of the ODC C terminus to generate a second recognition element.

  • Keywords:

    • antizyme,
    • ornithine decarboxylase,
    • proteasome,
    • protein degradation,
    • ubiquitin