| First Author | Yan J | Year | 2013 |
| Journal | Cell | Volume | 152 |
| Issue | 1-2 | Pages | 304-15 |
| PubMed ID | 23332762 | Mgi Jnum | J:193499 |
| Mgi Id | MGI:5468623 | Doi | 10.1016/j.cell.2012.12.021 |
| Citation | Yan J, et al. (2013) Inactivation of BAD by IKK inhibits TNFalpha-induced apoptosis independently of NF-kappaB activation. Cell 152(1-2):304-15 |
| abstractText | The IkappaB kinase complex (IKK) is a key regulator of immune responses, inflammation, cell survival, and tumorigenesis. The prosurvival function of IKK centers on activation of the transcription factor NF-kappaB, whose target gene products inhibit caspases and prevent prolonged JNK activation. Here, we report that inactivation of the BH3-only protein BAD by IKK independently of NF-kappaB activation suppresses TNFalpha-induced apoptosis. TNFalpha-treated Ikkbeta(-/-) mouse embryonic fibroblasts (MEFs) undergo apoptosis significantly faster than MEFs deficient in both RelA and cRel due to lack of inhibition of BAD by IKK. IKK phosphorylates BAD at serine-26 (Ser26) and primes it for inactivation. Elimination of Ser26 phosphorylation promotes BAD proapoptotic activity, thereby accelerating TNFalpha-induced apoptosis in cultured cells and increasing mortality in animals. Our results reveal that IKK inhibits TNFalpha-induced apoptosis through two distinct but cooperative mechanisms: activation of the survival factor NF-kappaB and inactivation of the proapoptotic BH3-only BAD protein. |
