Activation of the interferon-inducible enzymes, 2',5'-oligoadenylate synthetase and PKR by human T-cell leukemia virus type I Rex-response element.
In vitro-synthesized human T-cell leukemia virus type 1 (HTLV-I) Rex response element (Rex-RE) activates the interferon-induced 2',5'-oligoadenylate synthetase (2-50AS) in a dose-dependent manner. In addition, Rex-RE at 1 microgram/ml activates a second interferon-induced enzyme, p68 kinase (PKR); however, at 50 micrograms/ml, Rex-RE inhibits PKR activity. Poly(rl)-poly(rC) (10 micrograms/ml) dissociates the ribonucleoprotein complexes, Rex-RE/2-5OAS, or Rex-RE/PKR, whereas poly(rC) (100 micrograms/ml) does not, indicating the presence of high affinity interactions between Rex-RE and these two enzymes. To further characterize the interaction of Rex-RE with 2-5OAS and PKR, [32P]Rex-RE was uv-cross-linked to 2-5OAS and PKR present in interferon-treated HeLa cell extracts. The affinity of Rex-RE to highly purified 40-kDa human recombinant 2-5OAS was determined to be Kd = 4.7 nM. The relevance of these results to the pathogenesis of HTLV-I-associated adult T-cell leukemia/lymphoma is discussed.
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
E
E
Mordechai
N
N
Kon
E E
EE
Henderson
R J
RJ
Suhadolnik
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis* / Q000302:isolation & purification; D003432:Cross-Linking Reagents; D004305:Dose-Response Relationship, Drug; D004722:Endoribonucleases; D004789:Enzyme Activation; D004790:Enzyme Induction; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007700:Kinetics; D011066:Poly C / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000302:isolation & purification; D012367:RNA, Viral / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D043244:Ribonuclease III; D014466:Ultraviolet Rays; D019892:eIF-2 Kinase
D003432:Cross-Linking Reagents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011066:Poly C; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; D043244:Ribonuclease III; D011070:Poly I-C