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 language | English (US) |
|---|---|
| Pages (from-to) | 34410-34418 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 287 |
| Issue number | 41 |
| DOIs | |
| State | Published - Oct 5 2012 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
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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 journal › Article
}
TY - JOUR
T1 - Serine 123 phosphorylation modulates p21 protein stability and activity by suppressing ubiquitin-independent proteasomal degradation
AU - Chen, Xiangling
AU - Zhang, Jin
AU - Zhang, Min
AU - Liu, Shou
AU - Yan, Wensheng
AU - Jung, JinHyuk
AU - Chen, Xinbin
PY - 2012/10/5
Y1 - 2012/10/5
N2 - 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.
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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UR - http://www.scopus.com/inward/citedby.url?scp=84867240307&partnerID=8YFLogxK
U2 - 10.1074/jbc.M112.384990
DO - 10.1074/jbc.M112.384990
M3 - Article
C2 - 22908227
AN - SCOPUS:84867240307
VL - 287
SP - 34410
EP - 34418
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 41
ER -