| First Author | Song L | Year | 2006 |
| Journal | J Cell Biol | Volume | 175 |
| Issue | 4 | Pages | 607-17 |
| PubMed ID | 17116751 | Mgi Jnum | J:119008 |
| Mgi Id | MGI:3701009 | Doi | 10.1083/jcb.200602149 |
| Citation | Song L, et al. (2006) IKKbeta programs to turn on the GADD45alpha-MKK4-JNK apoptotic cascade specifically via p50 NF-kappaB in arsenite response. J Cell Biol 175(4):607-17 |
| abstractText | Cross talk between NF-kappaB and c-Jun N-terminal kinases (JNKs) has been implicated in the cell life and death decision under various stresses. Functional suppression of JNK activation by NF-kappaB has recently been proposed as a key cellular survival mechanism and contributes to cancer cells escaping from apoptosis. We provide a novel scenario of the proapoptotic role of IkappaB kinase beta (IKKbeta)-NF-kappaB, which can act as the activator of the JNK pathway through the induction of GADD45alpha for triggering MKK4/JNK activation, in response to the stimulation of arsenite, a cancer therapeutic reagent. This effect of IKKbeta-NF-kappaB is dependent on p50 but not the p65/relA NF-kappaB subunit, which can increase the stability of GADD45alpha protein through suppressing its ubiquitination and proteasome-dependent degradation. IKKbeta-NF-kappaB can therefore either activate or suppress the JNK cascade and consequently mediate pro- or antiapoptotic effects, depending on the manner of its induction. Furthermore, the NF-kappaB p50 subunit can exert a novel regulatory function on protein modification independent of the classical NF-kappaB transcriptional activity. |
