Disease relevance of POT1

• Finally, ectopic expression of hTERT in one HTLV-1 T cell line induces a marked decrease in the transcription of the POT1 gene [1].
• Thus, we examined POT1 mRNA expression in 51 gastric cancer (GC) tissues and evaluated telomere length and 3' telomeric overhang signals in 20 of the 51 GC tissues [2].

High impact information on POT1

• This regulation can take place at the telomere terminus, involving single-stranded DNA-binding proteins (POT1 in humans and Cdc13 in budding yeast), which have been proposed to contribute to the recruitment of telomerase and may also regulate the extent or frequency of elongation [3].
• Human telomeres are protected by shelterin, a complex that includes the POT1 single-stranded DNA binding protein [4].
• Deletion of the fission yeast pot1+ gene has an immediate effect on chromosome stability, causing rapid loss of telomeric DNA and chromosome circularization [5].
• In human cells, the loading of POT1 to telomeric ssDNA controls telomerase-mediated telomere elongation [6].
• PTOP interacts with POT1 and regulates its localization to telomeres [6].

Biological context of POT1

• Disruption of POT1-TPP1 interaction by dominant negative TPP1 expression or RNA interference (RNAi) resulted in telomere-length alteration and DNA damage responses [7].
• We conclude that hPot1 protects chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation [8].
• The telomeric single-strand DNA binding protein protection of telomeres 1 (POT1) protects telomeres from rapid degradation in Schizosaccharomyces pombe and has been implicated in positive and negative telomere length regulation in humans [9].
• POT1 overexpression protected against TRF2(DeltaBDeltaM)-induced loss of telomeric single-stranded overhangs, chromosomal instability, and senescence [10].
• Down-regulation of POT1 (T/n < 0.5) was observed more frequently in stage I/II GC (52.4%, 11 of 21) than in stage III/IV GC (23.3%, 7 of 30; P = 0.033), whereas up-regulation of POT1 (T/n > 2.0) was observed more frequently in stage III/IV GC (33.3%, 10 of 30) than in stage I/II GC (9.5%, 2 of 21; P = 0.048) [2].

Anatomical context of POT1

• Reduced POT1 expression was observed in GC cell lines with telomeres shortened by treatment with azidothymidine [2].
• Quantitative reverse transcription-PCR analysis showed that POT1 expression levels in the tumor relative to those in nonneoplastic mucosa (T/N ratio) were significantly higher in stage III/IV tumors than in stage I/II tumors (P = 0.005) [2].

Associations of POT1 with chemical compounds

• The cells grow normally in tamoxifen, but drug removal causes loss of POT1 from the telomere, rapid cell cycle arrest, and eventual cell death [11].
• The chymotrypsin was inactivated by DFP, and was inhibited by chymostatin and the chymotrypsin inhibitor, POT-1 [12].

Physical interactions of POT1

• Furthermore, POT1 binding was regulated by the TRF1 complex in response to telomere length [13].
• The treatment of human EcR293 cells by telomestatin induces a dramatic and rapid delocalization of POT1 from its normal telomere sites but does not affect the telomere localization of the double-stranded telomere-binding protein TRF2 [14].
• TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres [15].

Regulatory relationships of POT1

• We therefore generated a conditional cell line that lacks wild-type POT1 but expresses an estrogen receptor-POT1 fusion [11].
• Thus, depending on its location relative to the DNA 3'-end, hPOT1 can either inhibit telomerase action or form a preferred substrate for telomerase [16].

Other interactions of POT1

• Furthermore, expression of the respective interaction domains on PTOP and POT1 alone extended telomere length in human cells [6].
• POT1 as a terminal transducer of TRF1 telomere length control [13].
• Next, the down-regulation of hTERT transcription by Tax in HTLV-1 transformed or in Tax-expressing T lymphocytes is found to correlate with a significant increase of TRF2 and/or Pot1 mRNAs [1].
• We found that TRF1 and TRF2 are overexpressed in in vivo patient's samples from ATL but not asymptomatic carriers, while levels of POT1 expression did not specifically increase in ATL [17].
• Chromosome telomeres of humans and many model organisms contain a structure called a t-loop, which is maintained by TERF, TINF2, Pot1, and other proteins [18].

Analytical, diagnostic and therapeutic context of POT1

• Using indirect immunofluorescence, we show here that epitope-tagged hPot1 localizes to telomeres in interphase nuclei of human cells, consistent with a direct role in telomere end protection [19].

References