| First Author | Huang X | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 40 | Pages | 29401-13 |
| PubMed ID | 17686781 | Mgi Jnum | J:125379 |
| Mgi Id | MGI:3758392 | Doi | 10.1074/jbc.M702261200 |
| Citation | Huang X, et al. (2007) Blockade of Tumor Necrosis Factor-induced Bid Cleavage by Caspase-resistant Rb. J Biol Chem 282(40):29401-13 |
| abstractText | Tumor necrosis factor-alpha (TNF) activates caspase-8 to cleave effector caspases or Bid, resulting in type-1 or type-2 apoptosis, respectively. We show here that TNF also induces caspase-8-dependent C-terminal cleavage of the retinoblastoma protein (Rb). Interestingly, fibroblasts from Rb(MI/MI) mice, in which the C-terminal caspase cleavage site is mutated, exhibit a defect in Bid cleavage despite caspase-8 activation. Recent results suggest that TNF receptor endocytosis is required for the activation of caspase-8. Consistent with this notion, inhibition of V-ATPase, which plays an essential role in acidification and degradation of endosomes, specifically restores Bid cleavage in Rb(MI/MI) cells. Inhibition of V-ATPase sensitizes Rb(MI/MI) but not wild-type fibroblasts to TNF-induced apoptosis and stimulates inflammation-associated colonic apoptosis in Rb(MI/MI) but not wild-type mice. These results suggest that Rb cleavage is required for Bid cleavage in TNF-induced type-2 apoptosis, and this requirement can be supplanted by the inhibition of V-ATPase. |
