Propensity for HBZ-SP1 isoform of HTLV-I to inhibit c-Jun activity correlates with sequestration of c-Jun into nuclear bodies rather than inhibition of its DNA-binding activity

Journal Article · Tue Sep 01 00:00:00 EDT 2009 · Virology

DOI:https://doi.org/10.1016/j.virol.2009.06.027· OSTI ID:21357535

Clerc, Isabelle ^[1]; Hivin, Patrick ^[1]; Rubbo, Pierre-Alain ^[1]; Lemasson, Isabelle ^[2]; Barbeau, Benoit ^[3]; Mesnard, Jean-Michel ^[1]

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1. Universite Montpellier 1, Centre d'etudes d'agents Pathogenes et Biotechnologies pour la Sante (CPBS) (France)
2. East Carolina University, Department of Microbiology and Immunology, North Carolina (United States)
3. Universite du Quebec a Montreal, Departement des sciences biologiques, Montreal (Canada)

HTLV-I bZIP factor (HBZ) contains a C-terminal zipper domain involved in its interaction with c-Jun. This interaction leads to a reduction of c-Jun DNA-binding activity and prevents the protein from activating transcription of AP-1-dependent promoters. However, it remained unclear whether the negative effect of HBZ-SP1 was due to its weak DNA-binding activity or to its capacity to target cellular factors to transcriptionally-inactive nuclear bodies. To answer this question, we produced a mutant in which specific residues present in the modulatory and DNA-binding domain of HBZ-SP1 were substituted for the corresponding c-Fos amino acids to improve the DNA-binding activity of the c-Jun/HBZ-SP1 heterodimer. The stability of the mutant, its interaction with c-Jun, DNA-binding activity of the resulting heterodimer, and its effect on the c-Jun activity were tested. In conclusion, we demonstrate that the repression of c-Jun activity in vivo is mainly due to the HBZ-SP1-mediated sequestration of c-Jun to the HBZ-NBs.

• OSTI ID: 21357535
• Journal Information: Virology, Vol. 391, Issue 2; Other Information: DOI: 10.1016/j.virol.2009.06.027; PII: S0042-6822(09)00359-6; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
60 APPLIED LIFE SCIENCES
AMINO ACIDS
DNA
INTERACTIONS
LEUKEMIA VIRUSES
MUTANTS
PROTEINS
TRANSCRIPTION
CARBOXYLIC ACIDS
MICROORGANISMS
NUCLEIC ACIDS
ONCOGENIC VIRUSES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PARASITES
VIRUSES