TLP1: A Gene Encoding a Protein Component of Mammalian Telomerase Is a Novel Member of WD Repeats Family

Abstract

We have cloned and characterized the rat telomerase protein component 1 gene (TLP1), which is related to the gene for Tetrahymena p80. The cDNA encodes a 2629 amino acid sequence and produces the TLP1 proteins p240 and p230. The anti-TLP1 antibody specifically immunoprecipitated the telomerase activity. Moreover, p240 and p230 were copurified with telomerase activity in a series of extensive purification experiments. These results strongly suggest that the TLP1 proteins are components of, or are closely associated with, the rat telomerase. A pulse-chase experiment showed that p240 is modified to p230 in vivo. p230 was the dominant form in telomerase-positive cells, suggesting that modification of the TLP1 protein may regulate telomerase activity in vivo.

Combination therapy of malignant glioma cells with 2-5A-antisense telomerase RNA and recombinant adenovirus p53

“…They reduced telomerase activity and tumor growth to some extent. Recently, two additional components of the human telomerase were identified: the telomerase-associated protein (TEP1) 35,36 and the telomerase catalytic subunit or telomerase reverse transcriptase (hTERT). 37,38 Although hTR and hTERT are essential for telomerase activity, the expression of hTERT is closely associated with telomerase activity.…”

Mechanisms of cell immortalization mediated by EB viral activation of telomerase in nasopharyngeal carcinoma

“…The core telomerase enzyme contains an RNA moiety and a protein subunit. Human telomerase RNA (hTERC) comprises 450 nucleotides, whereas the protein component hTERT is a polypeptide of 1132 amino acid residues [41][42][43][44]. Being the catalyst interacting with both hTERC and telomeric DNA, hTERT contains four major regions: an N-terminal regulatory (R) domain, RNA-binding (RB) domain, reverse transcription (RT) domain and C-terminal dimerization domain [45].…”

Molecular interactions between telomerase and the tumor suppressor protein p53 in vitro

“…The protein subunits of telomerase include telomerase reverse transcriptase (TERT) and telomerase associated protein 1 (TEP1). TERT is the catalytic subunit of telomerase Harrington et al, 1997b;Kilian et al, 1997;Lingner and Cech, 1996;Lingner et al, 1997;Meyerson et al, 1997;Nakamura et al, 1997;Nakayama et al, 1998), whereas TEP1 has been shown to co-purify with telomerase activity and bind to both telomerase RNA and TERT (Harrington et al, 1997a,b;Nakayama et al, 1997).…”

“…These data suggest that the catalytic activity of hTERT does not always correlate with telomerase function in cells, and some structures of hTERT other than those required for the catalytic activity are also essential for telomerase function in vivo probably through interactions with other molecules. Identi®cations of telomerase interacting proteins and roles of other protein components of telomerase complex such as hTEP1 (Harrington et al, 1997a;Nakayama et al, 1997) and Tetrahymena p95 (Collins et al, 1995) in the regulation of telomerase activity are therefore of importance in our understandings of the control mechanisms of telomerase activity in human cancer.…”