Proteasome-mediated degradation of p21 via N-terminal ubiquitinylation

Joanna Bloom, Virginia Amador, Francesca Bartolini, George DeMartino, Michele Pagano

Research output: Contribution to journalArticle

240 Citations (Scopus)

Abstract

We examined the mechanism responsible for the degradation of p21, a negative regulator of the cell division cycle. We found that p21 proteolysis requires functional ubiquitin and Nedd8 systems. Ubiquitinylated forms of p21 and p21(K0), a p21 mutant missing all lysines, are detected in vivo and in vitro, showing that the presence of lysines is dispensable for p21 ubiquitinylation. Instead, the free amino group of the N-terminal methionine of p21 is a site for ubiquitinylation in vivo. Although wild-type p21 is more abundantly ubiquitinylated than p21(K0) mutant due to the presence of internal lysine residues, their rates of proteolysis are indistinguishable. These results demonstrate that proteasomal degradation of p21 is regulated by the ubiquitin pathway and suggest that the site of the ubiquitin chain is critical in making p21 a competent substrate for the proteasome.

Original languageEnglish (US)
Pages (from-to)71-82
Number of pages12
JournalCell
Volume115
Issue number1
DOIs
StatePublished - Oct 3 2003

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Proteasome Endopeptidase Complex
Ubiquitin
Proteolysis
Lysine
Degradation
Methionine
Cell Cycle
Cells
Substrates

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Proteasome-mediated degradation of p21 via N-terminal ubiquitinylation. / Bloom, Joanna; Amador, Virginia; Bartolini, Francesca; DeMartino, George; Pagano, Michele.

In: Cell, Vol. 115, No. 1, 03.10.2003, p. 71-82.

Research output: Contribution to journalArticle

Bloom, Joanna ; Amador, Virginia ; Bartolini, Francesca ; DeMartino, George ; Pagano, Michele. / Proteasome-mediated degradation of p21 via N-terminal ubiquitinylation. In: Cell. 2003 ; Vol. 115, No. 1. pp. 71-82.
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