| First Author | Peacock JW | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 5 | Pages | 1222-34 |
| PubMed ID | 19103758 | Mgi Jnum | J:145719 |
| Mgi Id | MGI:3835888 | Doi | 10.1128/MCB.01660-08 |
| Citation | Peacock JW, et al. (2009) PTEN loss promotes mitochondrially dependent type II Fas-induced apoptosis via PEA-15. Mol Cell Biol 29(5):1222-34 |
| abstractText | Two distinct biochemical signals are delivered by the CD95/Fas death receptor. The molecular basis for the differential mitochondrially independent (type I) and mitochondrially dependent (type II) Fas apoptosis pathways is unknown. By analyzing 24 Fas-sensitive tumor lines, we now demonstrate that expression/activity of the PTEN tumor suppressor strongly correlates with the distinct Fas signals. PTEN loss-of-function and gain-of-function studies demonstrate the ability to interconvert between type I and type II Fas pathways. Importantly, from analyses of Bcl-2 transgenic Pten(+/-) mice, Pten haploinsufficiency converts Fas-induced apoptosis from a Bcl-2-independent to a Bcl-2-sensitive response in primary thymocytes and activated T lymphocytes. We further show that PTEN influences Fas signaling, at least in part, by regulating PEA-15 phosphorylation and activity that, in turn, regulate the ability of Bcl-2 to suppress Fas-induced apoptosis. Thus, PTEN is a key molecular rheostat that determines whether a cell dies by a mitochondrially independent type I versus a mitochondrially dependent type II apoptotic pathway upon Fas stimulation. |
