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Human Adrenocortical Dysplasia Homolog (Mouse) (ACD) interaction partners

1. shorter telomere length and downregulation of the major shelterin components TRF2 and TPP1 (ACD) leading to "telomere uncapping", might play a critical role in recurrent pregnancy loss.

2. show that TPP1 NOB is critical for telomerase function and demonstrate that the telomerase interaction surface on TPP1 is more elaborate than previously appreciated

3. is involved in glioblastoma radioresistance, likely through the modulation of telomerase activity, proliferation, and apoptosis.

4. A defective POT1-TPP1 complex leads to longer and fragile telomeres, which in turn promotes genomic instability and cancer.

5. several missense mutations in human cancers that disrupt the POT1C-TPP1 interaction, resulting in POT1 instability, were identified.

6. the human POT1-TPP1 complex is a processivity factor for telomerase

7. UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication

8. Altered expression of TPP1 might contribute to persistent proliferation of fibroblast-like synovial cells in rheumatoid arthritis.

9. 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

10. Blocking TPP1 S111 phosphorylation by mutating residue S111 led to reduced telomerase association and telomere shortening.

11. 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.

12. Elevated expression of TPP1 in human colorectal cancer cells could protect telomere from DNA damage and confer radioresistance.

13. Down-regulation of TPP1 induced cell apoptosis in telomerase-negative osteosarcoma cell line.

14. G-quadruplex formation of telomeres significantly enhances the ability of POT1/TPP1 to block RPA's access to telomeres.

15. TPP1 has recently emerged as a primary contributor in protecting telomere DNA and in recruiting telomerase to the telomere ends. (Review)

16. 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

17. TPP1 is a binding partner and substrate for the deubiquitinating enzyme USP7.

18. 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.

19. 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.

20. 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.

Mouse (Murine) Adrenocortical Dysplasia Homolog (Mouse) (ACD) interaction partners

1. show that TPP1 NOB is critical for telomerase function and demonstrate that the telomerase interaction surface on TPP1 is more elaborate than previously appreciated

2. 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.

3. shelterin protein TIN2 can protect chromosome ends as a TRF2-tethered TIN2/TPP1/POT1 complex that lacks a physical connection to TRF1

4. Mouse hematopoietic stem cells are acutely sensitive to inactivation of the shelterin gene Acd.

5. 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]

6. telomeric regulator is required for proper urogenital ridge differentiation, axial skeleton specification and limb patterning in mice.

7. Tpp1 is required for the protective function of Pot1 proteins.

8. Tumors from Acd(acd/acd) p53(+/-) mice show a striking switch from the classic spectrum of p53(-/-) mice toward carcinomas.