Disease relevance of TEP1

• PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells [1].
• The PTEN gene (also called MMAC1 and TEP1) at chromosome 10q23 is mutated in a variety of predominantly late-stage tumors and has been shown to suppress glioma cell growth in vitro and in vivo [2].
• The tumor suppressor gene PTEN (MMAC1/TEP1) is lost frequently in advanced prostate cancer (PCa) [3].
• Germline mutations in the tumor-suppressor gene PTEN (MMAC1, TEP1) are found in Cowden syndrome, which predisposes to hamartomas, breast cancer, trichilemmomas, and thyroid tumors of follicular epithelium [4].
• Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers [5].

Psychiatry related information on TEP1

• Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts [6].
• Emerging neuroprotective strategies for Alzheimer's disease: dietary restriction, telomerase activation, and stem cell therapy [7].
• Role of Ets/Id proteins for telomerase regulation in human cancer cells [8].
• Nuclear expression of SV40 LTag, possibly in concert with detectable telomerase activity, could be responsible for immortalisation of (pre)malignant clones, as suggested by the mesothelioma-specific latency period [9].
• Venture science: climbing the ladder to telomerase, cognitive therapy and in situ hybridization [10].

High impact information on TEP1

• Two distinguishing features of TERT are its stable association with the telomerase RNA and its ability to repetitively reverse transcribe the template segment of RNA [11].
• The maintenance of telomere repeats in most eukaryotic organisms requires telomerase, which consists of a reverse transcriptase (RT) and an RNA template that dictates the synthesis of the G-rich strand of telomere terminal repeats [11].
• In the last few years the number of known pols, including terminal transferase and telomerase, has increased to at least 19 [12].
• Substrates for telomerase are single-stranded oligonucleotides in vitro and chromosome ends in vivo [13].
• Telomerase is a ribonucleoprotein polymerase that specifically elongates telomeres [14].

Chemical compound and disease context of TEP1

• Telomerase activity was inhibited in a dose and time-dependent manner with the treatment of cisplatin for 24, 48, or 72 h in a concentration ranged from 0.8 to 50 microM in BEL-7404 human hepatoma cells [15].
• RT-PCR analysis revealed that TP1 was ubiquitously expressed in all G and carcinomas. hTR was expressed in 4 out of 15 G, in 2 out of 3 mPTC, in 5 out of 9 PTC, in 5 out of 9 FTC, in all oFTC and in 9 out of 12 UTC samples [16].
• Telomerase inhibition and telomere loss in BEL-7404 human hepatoma cells treated with doxorubicin [17].
• Telomerase activity has been linked to retinoid induction of tumor cell differentiation, and the patterns of telomerase expression are different in the 2 pathways of acute promyelocytic leukemia (APL) cell differentiation: the retinoic acid receptor 3 (RAR3)-dependent and the retinoic X receptor 3 (RXR3)-dependent pathways [18].
• Telomerase activity, estrogen receptors (alpha, beta), Bcl-2 expression in human breast cancer and treatment response [19].

Biological context of TEP1

• Recently, a novel phosphatase designated PTEN/MMAC1/TEP1 and located on chromosome 10q23.3 has been implicated as a new tumor suppressor gene in human cancer [20].
• Mutations in the tumor suppressor gene PTEN (MMAC1/TEP1) are associated with a large number of human cancers and several autosomal-dominant disorders [21].
• Germline mutations in PTEN (MMAC1/TEP1) are found in patients with Cowden syndrome, a familial cancer syndrome which is characterized by a high risk of breast and thyroid neoplasia [22].
• The PTEN (MMAC1/TEP1) tumor suppressor gene was recently isolated and mapped to human chromosome band 10q23 [23].
• Alternative splicing of the human PTEN/MMAC1/TEP1 gene [24].

Anatomical context of TEP1

• PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinomas and renal carcinoma cell lines [25].
• TEP1 mRNA was expressed in normal monocytes, but not granulocytes [26].
• We then assessed hTERT and TEP1 mRNA expression in CD34-positive cells cultured in vitro with growth factors [27].
• Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas [28].
• Telomere length is maintained, by the presence of telomerase activity, in the vast majority of primary tumours and stem cells, suggesting that telomere maintenance is essential for cellular immortalization [29].

Associations of TEP1 with chemical compounds

• Since the cardioprotective effect of estrogen itself has not been ruled out, we examined that of raloxifene, which has been classified as a selective estrogen receptor modulator, on the proliferation and telomerase activity of human umbilical vein endothelial cells (HUVECs) [30].
• Raloxifene increases proliferation and up-regulates telomerase activity in human umbilical vein endothelial cells [30].
• Raloxifene also induced the phosphorylation of Akt, and pretreatment with a phosphatidylinositol 3-kinase inhibitor, LY294002, significantly attenuated the raloxifene-induced telomerase activity [30].
• Geldanamycin had no effect on the reconstituted activity but partially reduced the stimulated activity of the reconstituted telomerase by the TIG3 cell extract, suggesting that Hsp90 may contribute to the stimulatory effect of the cellular components [31].
• Retinoic acid inhibits telomerase activity and downregulates expression but does not affect splicing of hTERT: correlation with cell growth rate inhibition in an in vitro cervical carcinogenesis/multidrug-resistance model [32].

Physical interactions of TEP1

• Both proteins specifically associated with telomerase activity in human cell extracts and bound hTERT in rabbit reticulocyte lysates independently of the telomerase RNA [33].
• Functional human telomerase complexes are minimally composed of the human telomerase RNA (hTR) and a catalytic subunit (human telomerase reverse transcriptase [hTERT]) containing reverse transcriptase (RT)-like motifs [34].
• Human TRF1-binding protein PinX1 inhibits telomerase activity [35].
• Nucleolin interacts with telomerase [36].
• Small-molecule-based identification of dynamic assembly of E2F-pocket protein-histone deacetylase complex for telomerase regulation in human cells [37].

Enzymatic interactions of TEP1

• The roles of telomerase in cellular immortality and tumor biology have catalyzed a significant interest in this unusual polymerase [38].
• In conclusion, PKC isoenzymes alpha, beta, delta, epsilon, zeta regulate telomerase activity in head and neck cancer cells by phosphorylating hTERT [39].
• On the other hand, the C-terminal truncated RFC inhibits the telomerase activity more than the N-terminal-deleted and full-length RFC p140 [40].
• The results showed that after treatment of HRT, VCR and VP-16 for 24 hours, the cell proliferation was inhibited, apoptosis was induced, and telomerase activity and the protein expression of phosphorylated ERK1/2 were down-regulated [41].

Regulatory relationships of TEP1

• The telomeric repeat binding factor TRF1 inhibits telomerase at telomeres in cis in a length-dependent manner to achieve telomere length homeostasis [42].
• Collectively, these data suggest that hTERT contains distinct anchor regions that cooperate to help regulate telomerase-mediated DNA recognition and elongation [43].
• The telomerase activity was enhanced by basic fibroblast growth factor (bFGF) [44].
• Our data show that the common expression of hTERT and HSP90 regulates telomerase activity in thyroid carcinomas [45].
• These results suggest that the differential abundance of truncated USF2 may regulate telomerase activity during lymphocyte activation [46].

Other interactions of TEP1

• A significant correlation between hTRT expression and telomerase activity was observed [28].
• Here we describe a novel Pin2/TRF1 binding protein, PinX1 that inhibits telomerase activity and affects tumorigenicity [47].
• The 5' half of hTR comprises the pseudoknot (core) domain, which includes the RNA template for telomere synthesis and a highly conserved pseudoknot that is required for telomerase activity [48].
• Modifying the interaction between Smad3 and TERT gene may, thus, lead to novel strategies to regulate telomerase [49].
• Human telomerase accelerates growth of lens epithelial cells through regulation of the genes mediating RB/E2F pathway [50].

Analytical, diagnostic and therapeutic context of TEP1

• Cryoelectron microscopy (cryoEM) and single-particle image reconstruction methods were used to determine the structure of nine recombinant vaults of various composition, as well as wild-type and TEP1-deficient mouse vaults [51].
• Comparative gene mapping of the human and mouse TEP1 genes, which encode one protein component of telomerases [52].
• In this study, we used heteroduplex analysis and direct sequencing analysis and identified three novel germline mutations in the PTEN/MMAC1/TEP1 coding sequence from unrelated individuals with CS [53].
• This TaqMan RT-PCR assay appears to be useful in determining the quantities of hTERT and TEP1 mRNAs in clinical specimens [54].
• In contrast, NSCLC metastasis-derived VL-7 cells remained telomerase and ALT negative up to high passage numbers and following transplantation in severe combined immunodeficient mice [55].

References