Serine 123 phosphorylation modulates p21 protein stability and activity by suppressing ubiquitin-independent proteasomal degradation

Xiangling Chen, Jin Zhang, Min Zhang, Shou Liu, Wensheng Yan, JinHyuk Jung, Xinbin Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The cyclin-dependent kinase inhibitor p21Waf1/Cip1 is a major regulator of the cell cycle and plays an important role in many cellular processes, including differentiation, stress response, apoptosis, and tumorigenesis. We previously cloned the gene encoding dog p21 and found that unlike its human ortholog, dog p21 is expressed as two isoforms, one high molecular mass band of 23 kDa and one low molecular mass band of 19 kDa. In the current study, we found that the high molecular mass band is hosphorylated, whereas the low molecular mass band is hypophosphorylated. Moreover, by generating multiple mutants of dog p21, we found that serine 123 and proline 124, which form a consensus site for proline-directed phosphorylation, are required for expression of the high molecular mass p21 isoform through phosphorylation at serine 123. Most importantly, we showed that serine 123 phosphorylation inhibits ubiquitin-independent proteasomal degradation of p21 protein and subsequently, prolongs p21 protein half-life and enhances the ability of p21 to suppress cell proliferation. Taken together, these data reveal that serine 123 phosphorylation modulates p21 protein stability and activity by suppressing ubiquitin-independent proteasomal degradation.

Original languageEnglish (US)
Pages (from-to)34410-34418
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number41
DOIs
StatePublished - Oct 5 2012

Fingerprint

Phosphorylation
Protein Stability
Molecular mass
Ubiquitin
Serine
Degradation
Dogs
Proline
Protein Isoforms
Proteins
Cyclin-Dependent Kinases
Gene encoding
Proteolysis
Half-Life
Cell proliferation
Corrosion inhibitors
Cell Cycle
Carcinogenesis
Cell Proliferation
Apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Serine 123 phosphorylation modulates p21 protein stability and activity by suppressing ubiquitin-independent proteasomal degradation. / Chen, Xiangling; Zhang, Jin; Zhang, Min; Liu, Shou; Yan, Wensheng; Jung, JinHyuk; Chen, Xinbin.

In: Journal of Biological Chemistry, Vol. 287, No. 41, 05.10.2012, p. 34410-34418.

Research output: Contribution to journalArticle

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AU - Zhang, Jin

AU - Zhang, Min

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AU - Yan, Wensheng

AU - Jung, JinHyuk

AU - Chen, Xinbin

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AB - The cyclin-dependent kinase inhibitor p21Waf1/Cip1 is a major regulator of the cell cycle and plays an important role in many cellular processes, including differentiation, stress response, apoptosis, and tumorigenesis. We previously cloned the gene encoding dog p21 and found that unlike its human ortholog, dog p21 is expressed as two isoforms, one high molecular mass band of 23 kDa and one low molecular mass band of 19 kDa. In the current study, we found that the high molecular mass band is hosphorylated, whereas the low molecular mass band is hypophosphorylated. Moreover, by generating multiple mutants of dog p21, we found that serine 123 and proline 124, which form a consensus site for proline-directed phosphorylation, are required for expression of the high molecular mass p21 isoform through phosphorylation at serine 123. Most importantly, we showed that serine 123 phosphorylation inhibits ubiquitin-independent proteasomal degradation of p21 protein and subsequently, prolongs p21 protein half-life and enhances the ability of p21 to suppress cell proliferation. Taken together, these data reveal that serine 123 phosphorylation modulates p21 protein stability and activity by suppressing ubiquitin-independent proteasomal degradation.

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