Human T-cell leukemia virus type 1 (HTLV-1) tax requires CADM1/TSLC1 for inactivation of the NF-κB inhibitor A20 and constitutive NF-κB signaling

PLoS Pathogens
Rajeshree PujariNoula Shembade

Abstract

Persistent activation of NF-κB by the Human T-cell leukemia virus type 1 (HTLV-1) oncoprotein, Tax, is vital for the development and pathogenesis of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). K63-linked polyubiquitinated Tax activates the IKK complex in the plasma membrane-associated lipid raft microdomain. Tax also interacts with TAX1BP1 to inactivate the NF-κB negative regulatory ubiquitin-editing A20 enzyme complex. However, the molecular mechanisms of Tax-mediated IKK activation and A20 protein complex inactivation are poorly understood. Here, we demonstrated that membrane associated CADM1 (Cell adhesion molecule1) recruits Ubc13 to Tax, causing K63-linked polyubiquitination of Tax, and IKK complex activation in the membrane lipid raft. The c-terminal cytoplasmic tail containing PDZ binding motif of CADM1 is critical for Tax to maintain persistent NF-κB activation. Finally, Tax failed to inactivate the NF-κB negative regulator ubiquitin-editing enzyme A20 complex, and activate the IKK complex in the lipid raft in absence of CADM1. Our results thus indicate that CADM1 functions as a critical scaffold molecule for Tax and Ubc13 to form a cellular complex with NEMO, TAX...Continue Reading

References

Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A TanakaM Hatanaka
Feb 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·W J GrossmanL Ratner
Jan 1, 1996·Annual Review of Immunology·A S Baldwin
May 23, 1998·Annual Review of Immunology·S GhoshE B Kopp
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·Y MurakamiR H Reeves
Mar 13, 2001·Annual Review of Immunology·M Yoshida
Mar 30, 2001·Nature Genetics·M KuramochiY Murakami
May 2, 2002·Cell·Sankar Ghosh, Michael Karin
Aug 16, 2003·Laboratory Investigation; a Journal of Technical Methods and Pathology·Akihiko ItoYukihiko Kitamura
Aug 20, 2003·International Journal of Cancer. Journal International Du Cancer·Takeshi FukamiYoshinori Murakami
Apr 20, 2004·The Journal of Biological Chemistry·Kuan-Teh JeangMordechai Aboud
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Sep 13, 2005·Oncogene·Shao-Cong Sun, Shoji Yamaoka
Sep 13, 2005·Oncogene·William W Hall, Masahiro Fujii
Apr 14, 2006·Molecular and Cellular Biology·Louise van der WeydenAllan Bradley
Jul 11, 2006·Retrovirology·Cynthia de la FuenteFatah Kashanchi
Mar 27, 2007·Nature Reviews. Cancer·Masao Matsuoka, Kuan-Teh Jeang

❮ Previous
Next ❯

Citations

Feb 2, 2016·Viruses·Jessica L MartinLouis M Mansky
Jan 10, 2018·Genes·Bruno R B PiresEliana Abdelhay
Nov 18, 2017·Annual Review of Immunology·Charles R M Bangham
May 4, 2018·The FEBS Journal·Edward William Harhaj, Chou-Zen Giam
Apr 23, 2016·PLoS Pathogens·Kiruthika ManivannanCharles R M Bangham
Mar 13, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan McCormackNoula Shembade
Aug 4, 2016·Oncotarget·Curtis D HodgeJ N Mark Glover
Jul 11, 2020·Pathogens·Suchitra Mohanty, Edward W Harhaj
Sep 25, 2017·Virchows Archiv : an International Journal of Pathology·Takeharu KatoKoichi Ohshima
Dec 15, 2019·Pathogens·Stefania FochiMaria Grazia Romanelli
May 4, 2016·Médecine sciences : M/S·Aurélien SchwobChloé Journo
Aug 10, 2019·Journal of Oncology·Yueshuo LiYa Cao
Mar 9, 2018·Frontiers in Microbiology·Stefania FochiMaria G Romanelli
Jun 28, 2019·Frontiers in Microbiology·Stefania FochiMaria Grazia Romanelli
Mar 14, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elaine Y ChungB Hilda Ye
Jul 9, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Kheerthana Duraivelan, Dibyendu Samanta
Aug 8, 2021·International Journal of Molecular Sciences·Greta ForlaniMaria Grazia Romanelli
Aug 17, 2021·Frontiers in Cell and Developmental Biology·Hongxu LiShuijun Zhang

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM-130

Methods Mentioned

BETA
ubiquitination
co-immunoprecipitation
immunoprecipitations
co-IPs
fluorescence imaging
confocal microscopy
immunoprecipitation
transfections
Assay
electrophoretic mobility shift assay

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.