| First Author | Khalil H | Year | 2015 |
| Journal | J Cell Sci | Volume | 128 |
| Issue | 18 | Pages | 3502-13 |
| PubMed ID | 26224876 | Mgi Jnum | J:233104 |
| Mgi Id | MGI:5780784 | Doi | 10.1242/jcs.174409 |
| Citation | Khalil H, et al. (2015) The caspase-3-p120-RasGAP module generates a NF-kappaB repressor in response to cellular stress. J Cell Sci 128(18):3502-13 |
| abstractText | The nuclear factor kappaB (NF-kappaB) transcription factor is a master regulator of inflammation. Short-term NF-kappaB activation is generally beneficial. However, sustained NF-kappaB might be detrimental, directly causing apoptosis of cells or leading to a persistent damaging inflammatory response. NF-kappaB activity in stressed cells needs therefore to be controlled for homeostasis maintenance. In mildly stressed cells, caspase-3 cleaves p120 RasGAP, also known as RASA1, into an N-terminal fragment, which we call fragment N. We show here that this fragment is a potent NF-kappaB inhibitor. Fragment N decreases the transcriptional activity of NF-kappaB by promoting its export from the nucleus. Cells unable to generate fragment N displayed increased NF-kappaB activation upon stress. Knock-in mice expressing an uncleavable p120 RasGAP mutant showed exaggerated NF-kappaB activation when their epidermis was treated with anthralin, a drug used for the treatment of psoriasis. Our study provides biochemical and genetic evidence of the importance of the caspase-3-p120-RasGAP stress-sensing module in the control of stress-induced NF-kappaB activation. |
