Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telomeres, the physical ends of eukaryotic chromosomes, are important to stabilize the chromosome and have a unique simple repetitive DNA sequence, TTAGGG in humans. In most normal somatic cells, telomere length becomes 50-100 bp shorter with every cell division, and the cells finally go into senescence, while most cancer cells have been reported to maintain the length and thus are immortalized. Telomeres are replicated by a special transcriptase, called telomerase, which is composed of a template RNA (hTR) and at least two component proteins: hTERT (hEST 2/hTRT) and hTEP 1 (hTLP 1/hTP1). In the present paper, I examined the status of telomerase activities in oral squamous cell carcinomas (OSCCs), precancerous lesions, and also cell lines established from OSCCs, by using a non-radioactive PCR-based TRAP (telomeric repeat amplification protocol) assay. Telomerase activities were detected in 23 of 30 OSCCs, 8 of 17 leukoplakias, 0 of 5 normal tissues, and in 8 of 8 OSCC cell lines and 0 of 5 normal human keratinocyte cultures. These results indicated that telomerase activity might have some association with carcinogenesis and might be used as a tumor marker in OSCC.
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PMID:[Telomerase activity in oral squamous cell carcinoma and leukoplakia]. 1132 1

Telomerase reverse transcriptase (TRT) is a tumor-associated antigen expressed in the vast majority of human tumors and is presently one of the most promising target candidates for a therapeutic cancer vaccine. TRT is also expressed at low level in selected tissues and should be considered a self antigen. In the present study we sought to develop cytotoxic T lymphocytes (CTL) responses directed against human (h)TRT peptides with low relative affinity for which the available repertoire is to be preferentially spared from tolerance. This was accomplished by using analogue peptides of hTRT whose relative affinity for the MHC was increased by a targeted (-->Tyr) substitution in position one. By immunizing HLA A2.1 transgenic mice with these analogue peptides, we identified one such low relative affinity peptide (p572) that is endogenously processed and presented by HLA A2.1 in tumor cells, and is recognized by specific CTL. We used the highly immunogenic analogue peptide to successfully induce TRT-specific CTL in cancer patients and normal donors. CTL against p572-lysed human and mouse tumor cells but not activated autologous B cells. This peptide represents, therefore, an important candidate component of a cancer vaccine based on a TRT substrate and validates the strategy of targeting peptides with low affinity for the MHC for cancer immunotherapy.
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PMID:Identification of a human telomerase reverse transcriptase peptide of low affinity for HLA A2.1 that induces cytotoxic T lymphocytes and mediates lysis of tumor cells. 1221 71