Temporal Control of TNFα Signaling by Miz1

  • Anning Lin
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)


The pro-inflammatory cytokine tumor necrosis factor (TNFα) regulates a wide range of biological activities, including inflammation, immune responses, apoptosis, and tumorigenesis mainly through its cytoplasm membrane receptor TNF-R1 complex 1 [6,7], which activates downstream effectors such as NF-κB, caspases and JNK. However, the control of TNF-R1 complex 1 activity is incompletely understood. We report here that the transcription factor zinc finger protein Mizl selectively inhibits TNFα-induced JNK activation in a transcription-independent manner and has to be removed upon TNFα stimulation. Our results suggest a de-repression model for TNFα-induced JNK activation.


Death Domain Protein Transcription Factor Zinc Finger Protein Factor Zinc Finger Factor Zinc Kinase SAPK 
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  1. 1.
    Cryns V, Yuan J (1998) Proteases to die for. Genes Dev 12:1551–1570CrossRefPubMedGoogle Scholar
  2. 2.
    Hsu H, Shu HB, Pan MG, Goeddel DV (1996) TRADD-TRAF2 and TRADD FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299–308CrossRefPubMedGoogle Scholar
  3. 3.
    Liu J, Zhao Y, Eilers M, Lin A (2009) Miz1 is a signal- and pathway-specific modulator or regulator (SMOR) that suppresses TNFα-induced JNK activation. PNAS Oct 7. [Epub ahead of print]Google Scholar
  4. 4.
    Micheau O, Tschopp J (2003) Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114:181–190CrossRefPubMedGoogle Scholar
  5. 5.
    Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R et al (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death—inducing signaling complex. Cell 85:817–827CrossRefPubMedGoogle Scholar
  6. 6.
    Tartaglia LA, Goeddel DV (1992). Two TNF receptors. Immunol Today 13:151–153CrossRefPubMedGoogle Scholar
  7. 7.
    Tracey KJ, Cerami A (1994) Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu Rev Med 45:491–503CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Ben May Department for Cancer ResearchUniversity of ChicagoChicagoUSA

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