Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 90 === Telomerase, a specialized ribonucleoprotein reverse transcriptase complex that directs the synthesis of telomeric DNA, is repressed in normal human somatic cells, but is activated in most cancers and immortal cells, indicating that telomerase plays an important role in carcinogenesis and cellular immortalization. Exactly how the telomerase activity is regulated in human cell is not yet known.
In a previous study, we have shown that telomerase activity is controlled by PKCζ in nasopharyngeal cancer (NPC076) cells. In this study, the mechanism for the involvement of PKCζ in the regulation of telomerase in NPC-076 cells was investigated. First, we addressed the question if PKCζ may interact and form a complex with telomerase. No telomerase activity was detected in the immunoprecipitates of cell extracts treated with antibodies against PKCζ. To test the hypothesis that PKCζ may control telomerase activity through a complex of Par3/Par6/Cdc42/Rac1, we examined the effects of dominant-negative mutants of Cdc42 (DN-Cdc42) or Rac1 (DN-Rac1) on telomerase activity. Transient expression of DN-Cdc42 or DN-Rac1 produced an inhibition of telomerase activity. Our results are consistent with the postulate that PKCζ may function though a Par3/Par6/Cdc42/Rac1 complex to regulate of telomerase activity in NPC076 cells.
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