Ref-1 protein enhances the IL-2-stimulated telomerase activity.
Telomerase is an important ribonucleoprotein enzyme involved in cellular proliferation and senescence. Activation of telomerase has been detected in a vast majority of human cancer cells. In this article, we demonstrated that Interleukin-2 (IL-2) which is the pivotal cytokine in the immune system could stimulate the activity of telomerase in the cultured BA/F3beta cells. It was also found that the level of IL-2-induced telomerase activity was decreased by the treatment with chemical oxidant in vitro. Since IL-2 stimulation produces a oxidative shift of the intracellular environment, the activation and maintenance of telomerase in this oxidative circumstance requires particular protection. Here we proved the redox factor-1 (Ref-1) protein was involved in this process. The addition of GST-Ref-1 protein increased the level of IL-2-induced telomerase activity in the TRAP assay, while elimination of the endogenous Ref-1 protein by immunodepletion decreased it. Consistent with these in vitro results, IL-2-induced telomerase activity could be enhanced by transient overexpression of Ref-1 protein in BA/F3beta cells. Taken together, these findings proved that Ref-1 protein benefits the activation of telomerase activity in the oxidative microenvironment of the BA/F3beta cells stimulated by IL-2.
Xu
Weijing
W
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Yan
Mingda
M
Sun
Lanying
L
Zheng
Zhongcheng
Z
Liu
Xinyuan
X
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002478:Cells, Cultured; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D004357:Drug Synergism; D015151:Immunoblotting; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D019098:Telomerase / Q000032:analysis / Q000378:metabolism*
D000906:Antibodies; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D019098:Telomerase; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase