| First Author | Strömblad S | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 16 | Pages | 13371-4 |
| PubMed ID | 11856728 | Mgi Jnum | J:124691 |
| Mgi Id | MGI:3722236 | Doi | 10.1074/jbc.C200044200 |
| Citation | Stromblad S, et al. (2002) Loss of p53 compensates for alpha v-integrin function in retinal neovascularization. J Biol Chem 277(16):13371-4 |
| abstractText | alpha(v)-Integrin antagonists block neovascularization in various species, whereas 20% of alpha(v)-integrin null mice are born with many normal looking blood vessels. Given that blockade of alpha(v)-integrins during angiogenesis induces p53 activity, we utilized p53 null mice to elucidate whether loss of p53 can compensate for alpha(v)-integrin function in neovascularization of the retina. Murine retinal vascularization was inhibited by systemic administration of an alpha(v)-integrin antagonist. In contrast, mice lacking p53 were refractory to this treatment, indicating that neovascularization in normal mice depends on alpha(v)-integrin-mediated suppression of p53. Blockade of alpha(v)-integrins during neovascularization resulted in an induction of p21(CIP1) in wild type and, surprisingly, in p53 null retinas, indicating that alpha(v)-integrin ligation regulates p21(CIP1) levels in a p53-independent manner. In conclusion, we demonstrate for the first time an in vivo intracellular mechanism for compensation of integrin function and that p53 and alpha(v)-integrins act in concert during retinal neovascularization. |
