Identification and characterization of HTLV-1 HBZ post-translational modifications.
Human T-cell leukemia virus type-1 (HTLV-1) is estimated to infect 15-25 million people worldwide, with several areas including southern Japan and the Caribbean basin being endemic. The virus is the etiological agent of debilitating and fatal diseases, for which there is currently no long-term cure. In the majority of cases of leukemia caused by HTLV-1, only a single viral gene, hbz, and its cognate protein, HBZ, are expressed and their importance is increasingly being recognized in the development of HTLV-1-associated disease. We hypothesized that HBZ, like other HTLV-1 proteins, has properties and functions regulated by post-translational modifications (PTMs) that affect specific signaling pathways important for disease development. To date, PTM of HBZ has not been described. We used an affinity-tagged protein and mass spectrometry method to identify seven modifications of HBZ for the first time. We examined how these PTMs affected the ability of HBZ to modulate several pathways, as measured using luciferase reporter assays. Herein, we report that none of the identified PTMs affected HBZ stability or its regulation of tested pathways.
Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, United States of America; Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America.
Nathan
N
Dissinger
Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, United States of America; College of Pharmacy, The Ohio State University, Columbus Ohio, United States of America.
Nikoloz
N
Shkriabai
Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, California, United States of America.
Sonja
S
Hess
Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, United States of America; Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America.
Jacob
J
Al-Saleem
Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, United States of America; College of Pharmacy, The Ohio State University, Columbus Ohio, United States of America.
Mamuka
M
Kvaratskhelia
Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, United States of America; Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America; Comprehensive Cancer Center and Solove Research Institute, Columbus, Ohio, United States of America; Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America.
Patrick L
PL
Green
D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D002460:Cell Line; D057809:HEK293 Cells; D015490:HTLV-I Infections / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D012191:Retroviridae Proteins; D015398:Signal Transduction / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics*
D050976:Basic-Leucine Zipper Transcription Factors; C479751:HBZ protein, human T-cell leukemia virus type I; D012191:Retroviridae Proteins; D014764:Viral Proteins