Regulation of telomerase activity and anti‐apoptotic function by protein–protein interaction and phosphorylation

@article{Haendeler2003RegulationOT,
  title={Regulation of telomerase activity and anti‐apoptotic function by protein–protein interaction and phosphorylation},
  author={Judith Haendeler and Jörg Hoffmann and Sandy Rahman and Andreas M Zeiher and Stefanie Dimmeler},
  journal={FEBS Letters},
  year={2003},
  volume={536}
}
The enzyme telomerase is necessary for the synthesis and maintenance of telomere length. The catalytic subunit, telomerase reverse transcriptase (TERT), is regulated by interaction with the 90 kDa heat shock protein (HSP90) and by Akt‐dependent phosphorylation. Here, we demonstrate that HSP90 and Akt physically interact with TERT. Treatment of cells with novobiocin, which blocks C‐terminal interaction of HSP90, disrupted HSP90 binding to Akt, induced Akt dephosphorylation and significantly… 
The Biochemical Role of the Heat Shock Protein 90 Chaperone Complex in Establishing Human Telomerase Activity*
TLDR
It is proposed that the hsp90-p23 complex fine tunes and stabilizes a functional telomerase structure, allowing primer loading and extension, and may play a role in loading telomersase onto the telomere.
hTERT phosphorylation by PKC is essential for telomerase holoprotein integrity and enzyme activity in head neck cancer cells
TLDR
KPC isoenzymes α, β, δ, ɛ, ζ regulate telomerase activity in head and neck cancer cells by phosphorylating hTERT, which is essential for telomersase holoenzyme integrity and function.
Regulation of Telomerase Through Transcriptional and Posttranslational Mechanisms
The enzyme telomerase is associated with nearly 90% of human cancers. To better understand telomerase at the molecular level, a number of proteins involved in its regulation, either directly or
The role of phosphorylation and DNA damage signalling in human telomerase regulation
TLDR
Results suggest that phosphorylation of hTERT does not impact on the properties of telomerase measured in this chapter, but effects on other functional aspects of telomersase or h TERT cannot be excluded.
Curcumin inhibits nuclear localization of telomerase by dissociating the Hsp90 co-chaperone p23 from hTERT.
TLDR
Results demonstrate that the interaction of the Hsp90-p23 complex with hTERT is critical for regulation of the nuclear localization of telomerase, and that down-regulation of hterT by curcumin involves dissociating the binding of h TERT with p23.
Hsp90 functions to balance the phosphorylation state of Akt during C2C12 myoblast differentiation.
TLDR
Findings indicate that Hsp90 functions to balance the phosphorylation state of Akt by modulating the ability ofAkt to be dephosphorylated by PP2Ac during C2C12 myoblast differentiation.
Transcriptional up-regulation of TERT and TERC necessarily not mean higher telomerase activity: A report of telomerase inhibition with higher transcription of TERT, TERC and TERF2 in A549 cells treated with staurosporine.
Targeting telomerase is one of the approaches to kill cancer cells since almost 90% cancer are telomerase-positive. TERT and TERC are essential subunits of telomerase and a number of reports
Telomerase Biogenesis and Activities from the Perspective of Its Direct Interacting Partners
TLDR
The goal is to review the comprehensive spectrum of TERT pro-malignant activities, both telomeric and non-telomeric, which may explain the prevalence of its upregulation in cancer.
Disruption of an hTERT–mTOR–RAPTOR protein complex by a phytochemical perillyl alcohol and rapamycin
TLDR
Findings provide convincing evidence for mTOR-mediated regulation of hTERT in DU145 cells and establish an additional mechanism by which these agents decrease telomerase activity.
Nuclear Protein Tyrosine Phosphatase Shp-2 Is One Important Negative Regulator of Nuclear Export of Telomerase Reverse Transcriptase*
TLDR
It is demonstrated that H2O2-induced nuclear export of TERT was abolished in Src, Fyn, and Yes-deficient embryonic fibroblasts and one potential negative regulator of this export process is the protein tyrosine phosphatase Shp-2 (Shp- 2), which can counteract activities of the Src kinase family.
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