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ISSN
1672-9145
Acta Biochim Biophys Sin
2005, 37(1): 32–38
CN 31-1940/Q
Transcript Regulation of Human Telomerase Reverse Transcriptase by
c-myc and mad1
Lin ZOU#, Peng-Hui ZHANG, Chun-Li LUO, and Zhi-Guang TU*
Faculty of Laboratory Medicine, Chongqing University of Medical
Sciences, Chongqing 400016, China
Abstract Telomerase activity is highly positive
correlated to most malignant neoplasms. Human telomerase reverse transcriptase
(hTERT) is the rate-limiting factor of telomerase activity. Recent studies have
shown that the expression of hTERT is mainly determined by its transcript
regulation. Among the transcript regulation factors of hTERT, c-myc and mad1
are well known. Here, we constructed c-myc and mad1 eukaryotic
expression vectors, then co-transfected them with the wild-type (Tw) or mutant hTERT
promoter (Td) luciferase reporter plasmid, which were double-mutated in the
E-box sequences from CACGTG to CACCTG of Tw. The change of luciferase
activity in different cells was detected. The results showed that Tw was
obviously activated in T24 and EJ bladder cancer cells, but not in normal
fibrocytes. c-myc and mad1 had positive and negative effects respectively on
the Tw transcript in a dose-dependent manner, while the roles of c-myc and mad1
in regulating the Td transcript were reversed. c-myc combined with mad1 can
down-regulate Tw but not Td. These observations indicate that c-myc and mad1
can regulate the hTERT transcript in a different manner in hTERT positive
cells, but not in normal cells. This may provide an insight into some
telomerase-related carcinogenesis mechanisms.
Key words c-myc; mad1; hTERT promoter;
transcript regulation
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Received: September 29, 2004 Accepted: December 13,
2004
This work was supported by the grants from the National Natural
Science Foundation of China (No. 30400166) and Chongqing Education Committee
(No. 200120)
# Present address: Institute of Biochemistry
and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy
of Sciences, Shanghai 200031, China
*Corresponding author: Tel, 86-23-6848-5065; Fax, 86-23-6848-5005;
E-mail, [email protected]