The hTERTalpha splice variant is a dominant negative inhibitor of telomerase activity. Export

@article{citeulike:1269303, abstract = {The telomerase catalytic subunit (hTERT) is an essential component of the holoenzyme complex that adds telomeric repeats to the ends of human chromosomes. Maintenance of telomeres by telomerase or another mechanism is required for cell immortalization, and loss of telomeric DNA has been proposed as a trigger for cellular senescence. Available evidence suggests that regulation of telomerase activity primarily depends on transcriptional control of hTERT. However, several human tissues as well as some normal cell strains have been shown to express low levels of hTERT mRNA even though they lack telomerase activity. We have previously identified six splice variants of hTERT, including a "deletion" variant (hTERTalpha) that is missing conserved residues from the catalytic core of the protein. Several of the deletion variants have been detected in normal and developing human tissues. We now show that hTERTalpha inhibits endogenous telomerase activity, which results in telomere shortening and chromosome end-to-end fusions. Telomerase inhibition induced a senescence-like state in HT1080 cells and apoptosis in a jejunal fibroblast cell line. These results suggest a possible role for hTERT splice variants in the regulation of telomerase activity.}, address = {Children's Medical Research Institute, Westmead, New South Wales, Australia.}, author = {Colgin, L. M. and Wilkinson, C. and Englezou, A. and Kilian, A. and Robinson, M. O. and Reddel, R. R.}, citeulike-article-id = {1269303}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11191109}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11191109}, issn = {1522-8002}, journal = {Neoplasia}, keywords = {alternatesplicing}, number = {5}, pages = {426--432}, posted-at = {2007-04-30 23:51:42}, priority = {2}, title = {The hTERTalpha splice variant is a dominant negative inhibitor of telomerase activity.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11191109}, volume = {2}, year = {2000} }

TY - JOUR ID - citeulike:1269303 L3 - citeulike-article-id:1269303 N2 - The telomerase catalytic subunit (hTERT) is an essential component of the holoenzyme complex that adds telomeric repeats to the ends of human chromosomes. Maintenance of telomeres by telomerase or another mechanism is required for cell immortalization, and loss of telomeric DNA has been proposed as a trigger for cellular senescence. Available evidence suggests that regulation of telomerase activity primarily depends on transcriptional control of hTERT. However, several human tissues as well as some normal cell strains have been shown to express low levels of hTERT mRNA even though they lack telomerase activity. We have previously identified six splice variants of hTERT, including a "deletion" variant (hTERTalpha) that is missing conserved residues from the catalytic core of the protein. Several of the deletion variants have been detected in normal and developing human tissues. We now show that hTERTalpha inhibits endogenous telomerase activity, which results in telomere shortening and chromosome end-to-end fusions. Telomerase inhibition induced a senescence-like state in HT1080 cells and apoptosis in a jejunal fibroblast cell line. These results suggest a possible role for hTERT splice variants in the regulation of telomerase activity. IS - 5 JF - Neoplasia SN - 1522-8002 AD - Children's Medical Research Institute, Westmead, New South Wales, Australia. EP - 432 TI - The hTERTalpha splice variant is a dominant negative inhibitor of telomerase activity. VL - 2 SP - 426 KW - alternatesplicing AU - Colgin, LM AU - Wilkinson, C AU - Englezou, A AU - Kilian, A AU - Robinson, MO AU - Reddel, RR PY - 2000///t UR - http://view.ncbi.nlm.nih.gov/pubmed/11191109 ER -