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Abreu, Aritonovska, Reichenbach, Cristofari, Culp, Terns, Lingner, Terns: TIN2-tethered TPP1 recruits human telomerase to telomeres in vivo. dans Molecular and cellular biology 2010
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is involved in glioblastoma radioresistance, likely through the modulation of telomerase activity, proliferation, and apoptosis.
A defective POT1-TPP1 complex leads to longer and fragile telomeres, which in turn promotes genomic instability and cancer.
several missense mutations in human cancers that disrupt the POT1C-TPP1 interaction, resulting in POT1 instability, were identified.
the human POT1-TPP1 complex is a processivity factor for telomerase
UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication
Altered expression of TPP1 might contribute to persistent proliferation of fibroblast-like synovial cells in rheumatoid arthritis.
seven separation-of-function mutations map to a patch of amino acids on the surface of TPP1, the TEL patch, that both recruits telomerase to telomeres and promotes high-processivity DNA synthesis
Blocking TPP1 S111 phosphorylation by mutating residue S111 led to reduced telomerase association and telomere shortening.
Telomere damage and reduced TPP1 dimerization as a result of Akt inhibition was also accompanied by diminished recruitment of TPP1 and POT1 to the telomeres.
Elevated expression of TPP1 in human colorectal cancer cells could protect telomere from DNA damage and confer radioresistance.
Down-regulation of TPP1 induced cell apoptosis in telomerase-negative osteosarcoma cell line.
G-quadruplex formation of telomeres significantly enhances the ability of POT1/TPP1 to block RPA's access to telomeres.
TPP1 has recently emerged as a primary contributor in protecting telomere DNA and in recruiting telomerase to the telomere ends. (Review)
TPP1 provides an essential step of telomerase activation as well as feedback regulation of telomerase by telomere length, which is necessary to determine the appropriate telomere length set point in human embryonic stem cells
TPP1 is a binding partner and substrate for the deubiquitinating enzyme USP7.
these data provide a molecular basis by which POT1-TPP1 increases the processivity of telomerase15. Further, we show that this increased processivity may arise from the dynamic sliding of POT1-TPP1 that induces fast translocation of telomerase.
Mutations have been identified in the TEN-domain of TERT that disrupt the interaction of telomerase with TPP1 in vivo and in vitro but have very little effect on the catalytic activity of telomerase.
The conservation between fission yeast Tpz1-Pot1 and human TPP1-POT1 interactions resulted in mapping a human melanoma-associated POT1 mutation (A532P) to the TPP1-POT1 interface.
that the insertion in fingers domain can mediate enzyme processivity and telomerase recruitment to telomeres in a TPP1-dependent manner
Binding of POT1-TPP1 unfolds telomere secondary structure to assist loading of additional heterodimers.
Analyses demonstrate that the majority of differentially expressed genes in acd mutant embryos are due to p53-dependent mechanisms and reflect the observed phenotypic differences between acd mutant and double mutant embryos.
shelterin protein TIN2 can protect chromosome ends as a TRF2-tethered TIN2/TPP1/POT1 complex that lacks a physical connection to TRF1
Mouse hematopoietic stem cells are acutely sensitive to inactivation of the shelterin gene Acd.
Mouse gene deletion experiments revealed DNA-damage-response pathways that threaten chromosome ends and how the components of the telomeric shelterin complex prevent activation of these pathways.[Shelterin]
telomeric regulator is required for proper urogenital ridge differentiation, axial skeleton specification and limb patterning in mice.
Tpp1 is required for the protective function of Pot1 proteins.
Tumors from Acd(acd/acd) p53(+/-) mice show a striking switch from the classic spectrum of p53(-/-) mice toward carcinomas.
This gene encodes a protein that is involved in telomere function. This protein is one of six core proteins in the telosome/shelterin telomeric complex, which functions to maintain telomere length and to protect telomere ends. Through its interaction with other components, this protein plays a key role in the assembly and stabilization of this complex, and it mediates the access of telomerase to the telomere. Multiple transcript variants encoding different isoforms have been found for this gene. This gene, which is also referred to as TPP1, is distinct from the unrelated TPP1 gene on chromosome 11, which encodes tripeptidyl-peptidase I.
POT1 and TIN2 organizing protein
, POT1 and TIN2-interacting protein
, TIN2 interacting protein 1
, adrenocortical dysplasia protein homolog
, adrenocortical dysplasia homolog (mouse)
, adrenocortical dysplasia protein