| First Author | Liu J | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 43 | Pages | 18279-84 |
| PubMed ID | 19815509 | Mgi Jnum | J:153745 |
| Mgi Id | MGI:4366188 | Doi | 10.1073/pnas.0906328106 |
| Citation | Liu J, et al. (2009) Miz1 is a signal- and pathway-specific modulator or regulator (SMOR) that suppresses TNF-alpha-induced JNK1 activation. Proc Natl Acad Sci U S A 106(43):18279-84 |
| abstractText | The proinflammatory cytokine TNF-alpha exerts its pleiotropic functions through activation of multiple downstream effectors, including JNK1. Yet, the underlying regulatory mechanism is incompletely understood. Here, we report that the transcription factor Myc-interacting zinc-finger protein 1 (Miz1) selectively suppresses TNF-alpha-induced JNK1 activation and cell death independently of its transcription activity. Proteomics analysis and yeast two-hybrid screening reveal that Miz1 is a JNK-associated protein. The TNF-alpha-induced activation of JNK1 is augmented in Miz1-deficient mouse embryonic fibroblasts (Miz1(-/-) MEFs), but the augmentation is abrogated by reintroduction of Miz1 or its transcription-deficient mutant. The regulation by Miz1 is highly specific, because it regulates TNF-alpha-induced TRAF2 K63-linked polyubiquitination. Neither JNK1 activation by IL-1beta or UV nor TNF-alpha-induced activation of p38, ERK, or IkappaB kinase complex is affected by the loss of Miz1. The TNF-alpha-induced cell death also is accelerated in Miz1(-/-) MEFs. Upon TNF-alpha stimulation, Miz1 is degraded rapidly by the proteasome, relieving its suppression on JNK1 activation. Thus, our results show that in addition to being a transcription factor Miz1 acts as a signal- and pathway-specific modulator or regulator that specifically regulates TNF-alpha-induced JNK1 activation and cell death. |
