A Lysine-to-Arginine Change Found in Natural Alleles of the Human T-Cell Lymphotropic/Leukemia Virus Type 1 p12I Protein Greatly Influences Its Stability
AUTOR(ES)
Trovato, Raffaella
FONTE
American Society for Microbiology
RESUMO
The HTLV-1 singly spliced open reading frame I protein, p12I, is highly unstable and appears to be necessary for persistent infection in rabbits. Here we demonstrate that p12I forms dimers through two putative leucine zipper domains and that its stability is augmented by specific proteasome inhibitors. p12I is ubiquitylated, and mutations of its unique carboxy-terminus lysine residue to an arginine greatly enhance its stability. Interestingly, analysis of 53 independent HTLV-1 strains revealed that the natural p12I alleles found in ex vivo samples of tropical spastic paraparesis-HTLV-1-associated myelopathy patients contain a Lys at position 88 in some cases, whereas arginine is consistently found at position 88 in HTLV-1 strains from all adult T-cell leukemia-lymphoma (ATLL) cases and healthy carriers studied. This apparent segregation of different alleles in tropical spastic paraparesis-HTLV-associated myelopathy and ATLL or healthy carriers may be relevant in vivo, since p12I binds the interleukin-2 receptor β and γc chains, raising the possibility that the two natural alleles might affect differently the regulation of these molecules.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=112727Documentos Relacionados
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