PMID: 9658126Jul 11, 1998Paper

Cytoplasmic forms of human T-cell leukemia virus type 1 Tax induce NF-kappaB activation

Journal of Virology
Christophe NicotC Z Giam

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) Tax targets I-kappaB alpha and I-kappaB beta for phosphorylation, ubiquitination, and proteasome-mediated degradation, causing the nuclear translocation of NF-kappaB/Rel proteins and transcription induction of many cellular genes. The mechanism by which a nuclear protein such as Tax stimulates I-kappaB phosphorylation and degradation remains unclear. Here, we describe two cytoplasmic mutants of Tax, designated TaxDeltaN81 and TaxDeltaN109, from which the domains important for cyclic AMP response element binding factor (CREB) and serum response factor (SRF) binding and nuclear transport have been removed. These mutants were unable to trans activate from the HTLV-1 21-bp repeats or the serum response element in the c-fos promoter. In contrast, they activated NF-kappaB reporters, suggesting that activation of NF-kappaB by Tax occurs in the cytoplasm. Incorporation of the nuclear localization signal (NLS) of the simian virus 40 large T antigen into TaxDeltaN81 and TaxDeltaN109 redirected both proteins predominantly to the nucleus yet did not restore trans activation via CREB or SRF. The NLS fusion had little effect on TaxDeltaN81 but reduced NF-kappaB trans activation by TaxDeltaN109, pos...Continue Reading

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Citations

Mar 9, 2007·The Journal of Biological Chemistry·Takahiro TsujiWilliam W Hall
Nov 24, 1999·The Journal of Biological Chemistry·A L Kimzey, W S Dynan
Oct 8, 2003·The Journal of Biological Chemistry·Kaili WuFatah Kashanchi
Apr 3, 2003·The Journal of Biological Chemistry·Timothy AlefantisBrian Wigdahl
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Jan 1, 1998·Hematology·F Ravandi-KashaniF J Giles
Nov 18, 2000·AIDS Research and Human Retroviruses·Y L KuoC Z Giam
Mar 22, 2002·Journal of Virology·Min-Hui LiangChou-Zen Giam
Sep 13, 2005·Oncogene·Fatah Kashanchi, John N Brady
Jan 22, 2005·The Journal of Biological Chemistry·Timothy AlefantisBrian Wigdahl
Mar 23, 2012·Immunological Reviews·Jonathan K Chan, Warner C Greene
Nov 9, 2010·Cancer Science·Keiyu YamamotoToshiki Watanabe
Apr 11, 2017·Acta Pharmacologica Sinica·Lan-Lan ZhangJi-Long Chen
Sep 26, 2001·Experimental Cell Research·D SaggioroL Chieco-Bianchi
Apr 29, 2008·Retrovirology·Rienk E JeeningaBen Berkhout

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