positive regulation of telomere maintenance via telomere lengthening
Definition
Target type: biologicalprocess
Any process that activates or increases the frequency, rate or extent of telomere maintenance via telomere lengthening. [GO_REF:0000058, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:23959892]
Positive regulation of telomere maintenance via telomere lengthening is a crucial biological process that ensures the stability and integrity of chromosomes, thereby promoting cellular longevity and preventing premature aging. Telomeres are protective caps at the ends of chromosomes, preventing degradation and fusion of DNA. With each cell division, telomeres naturally shorten due to the inability of DNA polymerase to fully replicate the ends of linear chromosomes. This gradual shortening contributes to cellular senescence, a state of irreversible cell cycle arrest, and ultimately, aging. However, some cells, such as stem cells and germ cells, possess mechanisms to counteract telomere shortening and maintain their replicative capacity.
Telomere lengthening, also known as telomere elongation, is the process of extending the length of telomeres. It is primarily achieved through the action of the enzyme telomerase, a reverse transcriptase that synthesizes repetitive DNA sequences (TTAGGG in humans) at the ends of chromosomes. Telomerase is a ribonucleoprotein complex consisting of a catalytic protein subunit (TERT) and a template RNA subunit (TERC). TERC acts as a template for the synthesis of the telomeric repeats, while TERT possesses the reverse transcriptase activity to extend the telomere using TERC as a guide.
The process of positive regulation of telomere maintenance via telomere lengthening involves a complex interplay of factors, including:
- **Telomerase expression and activity:** The expression and activity of telomerase are tightly regulated in different cell types. Stem cells and germ cells exhibit high levels of telomerase, allowing them to maintain telomere length and proliferate indefinitely. However, in most somatic cells, telomerase activity is suppressed, leading to gradual telomere shortening with each cell division.
- **Transcriptional and post-transcriptional regulation of telomerase:** The expression of telomerase is regulated at both the transcriptional and post-transcriptional levels. Transcription factors, such as MYC, c-MYB, and Sp1, can bind to the promoter region of the TERT gene, enhancing its transcription. Post-transcriptional regulation of telomerase involves factors like microRNAs and other regulatory proteins that can modulate its stability and translation.
- **Telomere binding proteins:** A variety of proteins, including shelterin complex components, bind to telomeres, contributing to their stability and regulating access to the telomere by telomerase. These proteins play crucial roles in protecting telomeres from degradation and promoting the recruitment of telomerase.
- **Cellular signaling pathways:** Several signaling pathways, including the PI3K/AKT pathway, MAPK pathway, and Wnt pathway, can modulate telomere length and telomerase activity. These pathways are influenced by various stimuli, including growth factors, stress, and cellular environment.
- **Environmental factors:** External factors like diet, exercise, and exposure to toxins can indirectly influence telomere maintenance through their effects on cellular signaling pathways and telomerase activity.
Dysregulation of telomere maintenance can have profound consequences. Excessive telomere lengthening can lead to uncontrolled cell proliferation and cancer development. Conversely, insufficient telomere lengthening can contribute to premature aging and age-related diseases. Understanding the complex mechanisms of telomere maintenance and regulation is crucial for developing strategies to combat aging and age-related diseases, promote cellular longevity, and potentially prevent cancer.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Serine-protein kinase ATM | A serine-protein kinase ATM that is encoded in the genome of human. [PRO:CNA] | Homo sapiens (human) |
Compounds (20)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| pd 173074 | aromatic amine; biaryl; dimethoxybenzene; pyridopyrimidine; tertiary amino compound; ureas | antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor; fibroblast growth factor receptor antagonist | |
| caffeine | purine alkaloid; trimethylxanthine | adenosine A2A receptor antagonist; adenosine receptor antagonist; adjuvant; central nervous system stimulant; diuretic; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; environmental contaminant; food additive; fungal metabolite; geroprotector; human blood serum metabolite; mouse metabolite; mutagen; plant metabolite; psychotropic drug; ryanodine receptor agonist; xenobiotic | |
| 2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one | 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first source | chromones; morpholines; organochlorine compound | autophagy inhibitor; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; geroprotector |
| schizandrin b | schizandrin B: a phytogenic antineoplastic agent with anti-inflammatory activity; isolated from Schisandra plant | ||
| thiourea | thiourea : The simplest member of the thiourea class, consisting of urea with the oxygen atom substituted by sulfur. Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS. | one-carbon compound; thioureas; ureas | antioxidant; chromophore |
| ku 55933 | 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one: specific inhibitor of the ataxia-telangiectasia mutated kinase ATM; structure in first source | ||
| cgk 733 | diarylmethane | ||
| nu 7026 | 2-(morpholin-4-yl)benzo(h)chromen-4-one: a radiosensitizing agent that inhibits DNA-dependent protein kinase; structure in first source | organic heterotricyclic compound; organooxygen compound | |
| nu 7441 | 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one: structure in first source | dibenzothiophenes | |
| ku-0060648 | dibenzothiophenes | ||
| dactolisib | dactolisib : An imidazoquinoline that is 3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinoline substituted at position 1 by a 4-(1-cyanoisopropyl)phenyl group and at position 8 by a quinolin-3-yl group. A dual PI3K/mTOR inhibitor used in cancer treatment. dactolisib: antineoplastic agent that inhibits both phosphatidylinositol 3-kinase and mTOR | imidazoquinoline; nitrile; quinolines; ring assembly; ureas | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; mTOR inhibitor |
| ku 60019 | |||
| cp 466722 | quinazolines | ||
| (3R)-4-[2-(1H-indol-4-yl)-6-(1-methylsulfonylcyclopropyl)-4-pyrimidinyl]-3-methylmorpholine | indoles | ||
| ve 821 | 3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide: an antineoplastic agent; structure in first source | aromatic amide | |
| torin 2 | torin 2 : A member of the class of pyridoquinolines that is benzo[h][1,6]naphthyridin-2-one carrying additional 3-(trifluoromethyl)phenyl and 6-aminopyridin-3-yl substituents at positions 1 and 9 respectively. It is a potent inhibitor of mTOR and exhibits anti-cancer properties. | aminopyridine; organofluorine compound; primary amino compound; pyridoquinoline | antineoplastic agent; mTOR inhibitor |
| byl719 | proline derivative | ||
| cc-115 | 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino(2,3-b)pyrazin-2(1H)-one: an mTOR kinase inhibitor; structure in first source | ||
| vx-970 | berzosertib: an ATR kinase inhibitor | sulfonamide | |
| etp-46464 | ETP-46464: inhibits ATM and Rad3-related kinase; structure in first source |