| First Author | Wu ZH | Year | 2010 |
| Journal | Mol Cell | Volume | 40 |
| Issue | 1 | Pages | 75-86 |
| PubMed ID | 20932476 | Mgi Jnum | J:165643 |
| Mgi Id | MGI:4837960 | Doi | 10.1016/j.molcel.2010.09.010 |
| Citation | Wu ZH, et al. (2010) ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress. Mol Cell 40(1):75-86 |
| abstractText | Activation of the transcription factor NF-kappaB by multiple genotoxic stimuli modulates cancer cell survival. This response is mediated by a conserved pathway involving the nuclear ATM kinase and cytoplasmic IkappaB kinase (IKK); however, the molecular link between them remains incompletely understood. Here we show that ATM activates the IKK kinase TAK1 in a manner dependent on IKKgamma/NEMO and ELKS (a protein rich in glutamate, leucine, lysine, and serine). K63-linked polyubiquitination of ELKS, dependent on the ubiquitin ligase XIAP and the conjugating enzyme UBC13, allows ELKS association with TAK1 via its ubiquitin-binding subunits TAB2/3. Although NEMO mutants defective in ubiquitin binding permit ATM-dependent TAK1 activation, they block NEMO association with ELKS and IKK activation. Thus, ATM- and NEMO-dependent ubiquitination of ELKS leads to the ubiquitin-dependent assembly of TAK1/TAB2/3 and NEMO/IKK complexes, resulting in IKK and NF-kappaB activation following genotoxic stimuli. |
