Abstract
We show in this study that PTEN regulates p53 protein levels and transcriptional activity through both phosphatase-dependent and -independent mechanisms. The onset of tumor development in p53+/-;Pten +/- mice is similar to p53-/- animals, and p53 protein levels are dramatically reduced in Pten-/- cells and tissues. Reintroducing wild-type or phosphatase-dead PTEN mutants leads to a significant increase in p53 stability. PTEN also physically associates with endogenous p53. Finally, PTEN regulates the transcriptional activity of p53 by modulating its DNA binding activity. This study provides a novel mechanism by which the loss of PTEN can functionally control "two" hits in the course of tumor development by concurrently modulating p53 activity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 117-130 |
| Number of pages | 14 |
| Journal | Cancer Cell |
| Volume | 3 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 1 2003 |
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ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research
Cite this
PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms. / Freeman, Daniel J.; Li, Andrew G.; Wei, Gang; Li, Heng Hong; Kertesz, Nathalie; Lesche, Ralf; Whale, Andrew D.; Martinez-Diaz, Hilda; Rozengurt, Nora; Cardiff, Robert; Liu, Xuan; Wu, Hong.
In: Cancer Cell, Vol. 3, No. 2, 01.01.2003, p. 117-130.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms
AU - Freeman, Daniel J.
AU - Li, Andrew G.
AU - Wei, Gang
AU - Li, Heng Hong
AU - Kertesz, Nathalie
AU - Lesche, Ralf
AU - Whale, Andrew D.
AU - Martinez-Diaz, Hilda
AU - Rozengurt, Nora
AU - Cardiff, Robert
AU - Liu, Xuan
AU - Wu, Hong
PY - 2003/1/1
Y1 - 2003/1/1
N2 - We show in this study that PTEN regulates p53 protein levels and transcriptional activity through both phosphatase-dependent and -independent mechanisms. The onset of tumor development in p53+/-;Pten +/- mice is similar to p53-/- animals, and p53 protein levels are dramatically reduced in Pten-/- cells and tissues. Reintroducing wild-type or phosphatase-dead PTEN mutants leads to a significant increase in p53 stability. PTEN also physically associates with endogenous p53. Finally, PTEN regulates the transcriptional activity of p53 by modulating its DNA binding activity. This study provides a novel mechanism by which the loss of PTEN can functionally control "two" hits in the course of tumor development by concurrently modulating p53 activity.
AB - We show in this study that PTEN regulates p53 protein levels and transcriptional activity through both phosphatase-dependent and -independent mechanisms. The onset of tumor development in p53+/-;Pten +/- mice is similar to p53-/- animals, and p53 protein levels are dramatically reduced in Pten-/- cells and tissues. Reintroducing wild-type or phosphatase-dead PTEN mutants leads to a significant increase in p53 stability. PTEN also physically associates with endogenous p53. Finally, PTEN regulates the transcriptional activity of p53 by modulating its DNA binding activity. This study provides a novel mechanism by which the loss of PTEN can functionally control "two" hits in the course of tumor development by concurrently modulating p53 activity.
UR - http://www.scopus.com/inward/record.url?scp=0041450058&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041450058&partnerID=8YFLogxK
U2 - 10.1016/S1535-6108(03)00021-7
DO - 10.1016/S1535-6108(03)00021-7
M3 - Article
C2 - 12620407
AN - SCOPUS:0041450058
VL - 3
SP - 117
EP - 130
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 2
ER -