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Telomerase
2015-06-19
azim58 - Telomerase Telomerase portal Facts about telomerase http://www4.utsouthwestern.edu/cellbio/shay-wright/intro/facts/sw_facts.htm l =========================================================================== an example telomere repeating sequence: TTAGGG telomere length: can be up to about 15,000 bp; in humans average telomere length is 10-15 kb (ref [Telomere Shortening in Human Diseases]) telomere loss per cell division: about 25-200 bp; 50-200 bp (ref [Telomere Shortening in Human Diseases]); 71-71 bp/year in lymphocytes (High-throughput telomere length quantification by FISH and its application to human population studies) Critically short length of telomeres: about 77 bp (1) -1: paper: The nature of telomere fusion and a definition of the critical telomere length in human cells --see also [what is the critical short length of telomeres] telomerase 10-20X more active in cancer cells -[brief calculation of telomere loss 07-20-2014d1317] ================= Structure of telomerase Nice paper on structure of telomerase -"C:\Users\Kurt Whittemore\Box Sync\DocDR\2014\09-22-2014d0952\A solution to the telomerase puzzle.pdf" --University of California Santa Cruz 2013 =========================================================================== books about telomerase -[Telomerase c chemistry, biology, and clinical applications 01-15-2014d1749] =========================================================================== historical figures involved with telomerase discoveries -Herman Muller, Elizabeth Blackburn, August Weissmann (around 1881), Hayflick (around 1961), Carol W. Greider (around the 80s) diseases associated with faulty telomerase holoenzyme complex or faulty telomeres -dyskeratosis congenita is caused by a mutation in the dyskerin protein. -Acquired aplastic anaemia -Idiopathic pulmonary fibrosis (IPF) -Cartilage hair hypoplasia (CHH) -Bloom syndrome -ataxia-telangiectasia -Nijmegen breakage syndrome -Fanconi anemia components of telomerase holoenzyme -TERT (protein part) --the TERT protein has at least different isoforms (3) -TERC or TR (RNA part) -DKC1 -other proteins? http://string-db.org/newstring_cgi/show_network_section.pl?taskId=wTgLx7RN_ 8qX&interactive=_unassigned&network_flavor=actions -here's a diagram of some other proteins interacting with TERT at the Artandi lab stanford webpage http://www.stanford.edu/group/artandi/telomerase.htm Super-active telomerase exists (Julian Chen at ASU has worked with this) centenarians and their offspring have longer telomeres compared to the telomeres of the whole population on average Interaction of telomerase with other proteins? If I remember correctly, telomerase can interact with other proteins to turn other genes on and off as well. I would be interested to know what other types of proteins and/or transcription factor proteins telomerase interacts with to do this. Can telomerase act as a transcription factor itself? I don't know. -Telomerase interacts with quite a few other proteins. see http://string-db.org/newstring_cgi/show_network_section.pl?taskId=wTgLx7RN_ 8qX&interactive=_unassigned&network_flavor=actions -TERT involved in Wnt signaling [Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins] -TERT acts as a RNA polymerase [Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins] -TERT involved in stem cell mobilization [Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins] TERT Complexes hTERT+hTERC -> telomerase activity -> telomere maintenance hTERT+RMRP -> RdRP activity -> chromatin maintenance? hTERT+BRG1 -> regulation of Wnt/beta-catenin signalling -> stem cell maintenance hTERT + other proteins? -> other activities? -> other functions? -Section 8.4 of Telomerase: Chemistry, biology, and clinical applications Factors affecting telomerase transcription? There are many factors that can influence the level of expression of telomerase in a cell. For example, I know that estrogen even binds to proteins which then either directly or indirectly influence how proteins bind to the promoter of telomerase and upregulate or downregulate telomerase expression. There are many other compounds besides estrogen that have an influence. I wish I knew much more about this. Post-translational modifications of telomerase Does telomerase get phosphorylated at various sites to enhance or reduce various functions as many other proteins do? Yes it does. Some of the phosphorylation sites can be found here http://www.phosphosite.org/proteinAction.do;jsessionid=71C94B3261C802ED99FA 94C29B195611?id=3829&showAllSites=false =========================================================================== companies that claim to lengthen or maintain telomeres Some research papers on telomerase portal 6-14-13 Organizations to measure telomeres Telomerase Research Paper by Mara ================== Telomerase expression not sufficient to maintain telomere length in cells and stem cells -Telomere and telomerase in stem cells paper (British journal of cancer 2007) ================== Effect of telomerase in quiescent non-dividing cells -Telomere dysfunction induces metabolic and mitochondrial compromise ==================== Do cancer cells have long or short telomeres? -According to Marinela Mendez, normal tumor cells have short telomeres because they divide so fast. Cancer stem cells have super long telomeres ================= -[How does health increase with increased telomerase expression] -[extra-telomeric roles of telomerase 02-23-2015d1214] =============== Questions -Why do K5-mTERT mice (telomerase overexpressing mice) develop more tumors, but then mice treated with telomerase gene therapy or mice that have telomerase activated after turning on a genetic switch (like in the Harvard paper titled "Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice") do not? Is it just because in the K5-mTERT mice the overexpression is constant, and in the other two cases it is temporary overexpression? --Perhaps the gene therapy mice don't get cancer because the AAVTERT is diluted out when cells proliferate... ---------------- See also -[Cancer portal 10-02-2014d1110] -[constant overexpression of telomerase portal 05-14-2015d1443] -[normal range of length for mouse telomeres 06-19-2015d1717]
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