TERF2IP

Summary

Gene Symbol: TERF2IP
Description: TERF2 interacting protein
Alias: DRIP5, RAP1, telomeric repeat-binding factor 2-interacting protein 1, TERF2-interacting telomeric protein 1, TRF2-interacting telomeric RAP1 protein, dopamine receptor-interacting protein 5, repressor/activator protein 1 homolog
Species: human
Products:     TERF2IP

Top Publications

  1. Li L, Wang S, Jezierski A, Moalim Nour L, Mohib K, Parks R, et al. A unique interplay between Rap1 and E-cadherin in the endocytic pathway regulates self-renewal of human embryonic stem cells. Stem Cells. 2010;28:247-57 pubmed publisher
    ..Here, we show that functional interactions between small GTPase Rap1 and the adhesion molecule E-cadherin uniquely regulate the self-renewal of human embryonic stem cells (hESCs)...
  2. Loayza D, de Lange T. POT1 as a terminal transducer of TRF1 telomere length control. Nature. 2003;423:1013-8 pubmed
  3. Liu D, Safari A, O Connor M, Chan D, Laegeler A, Qin J, et al. PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol. 2004;6:673-80 pubmed
    ..and ageing, and requires cooperation between a multitude of telomeric factors, including telomerase, TRF1, TRF2, RAP1, TIN2, Tankyrase, PINX1 and POT1 (refs 1-12)...
  4. Teo H, Ghosh S, Luesch H, Ghosh A, Wong E, Malik N, et al. Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-dependent gene expression. Nat Cell Biol. 2010;12:758-67 pubmed publisher
    We describe a genome-wide gain-of-function screen for regulators of NF-kappaB, and identify Rap1 (Trf2IP), as an essential modulator of NF-kappaB-mediated pathways...
  5. Yang D, Xiong Y, Kim H, He Q, Li Y, Chen R, et al. Human telomeric proteins occupy selective interstitial sites. Cell Res. 2011;21:1013-27 pubmed publisher
    Human telomeres are bound and protected by protein complexes assembled around the six core telomeric proteins RAP1, TRF1, TRF2, TIN2, TPP1, and POT1. The function of these proteins on telomeres has been studied extensively...
  6. Li B, Oestreich S, de Lange T. Identification of human Rap1: implications for telomere evolution. Cell. 2000;101:471-83 pubmed
    ..The data suggest that ancestral telomeres, like those of vertebrates, contained a TRF-like protein as well as Rap1. We propose that budding yeast preserved Rap1 at telomeres but lost the TRF component, possibly concomitant with a ..
  7. Kim H, Lee O, Xin H, Chen L, Qin J, Chae H, et al. TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs. Nat Struct Mol Biol. 2009;16:372-9 pubmed publisher
    ..Our findings indicate that an array of TRF2 molecules functions as a protein hub and regulates telomeres by recruiting different signaling molecules via a linear sequence code. ..
  8. Bombarde O, Boby C, Gomez D, Frit P, Giraud Panis M, Gilson E, et al. TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends. EMBO J. 2010;29:1573-84 pubmed publisher
    ..We found that (1) TRF2/RAP1 prevents C-NHEJ-mediated end fusion at the initial DNA-PK end binding and activation step and (2) DNA-PK ..
  9. O Connor M, Safari A, Liu D, Qin J, Songyang Z. The human Rap1 protein complex and modulation of telomere length. J Biol Chem. 2004;279:28585-91 pubmed
    ..These results indicate that hRap1 negatively regulates telomere length in vivo and suggest that the linker region of hRap1 may modulate the recruitment of negative regulators of telomere length. ..

More Information

Publications107 found, 100 shown here

  1. Katagiri K, Maeda A, Shimonaka M, Kinashi T. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat Immunol. 2003;4:741-8 pubmed
    The small GTPase Rap1 is a potent activator of leukocyte integrin. However, the regulatory mechanism involved is unknown. Here, we identify the Rap1 effector, RAPL, as an essential regulator in this activation...
  2. Tarsounas M, Muñoz P, Claas A, Smiraldo P, Pittman D, Blasco M, et al. Telomere maintenance requires the RAD51D recombination/repair protein. Cell. 2004;117:337-47 pubmed
    ..We conclude that RAD51D plays a dual cellular role in both the repair of DNA double-strand breaks and telomere protection against attrition and fusion. ..
  3. Ye J, Donigian J, Van Overbeek M, Loayza D, Luo Y, Krutchinsky A, et al. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J Biol Chem. 2004;279:47264-71 pubmed
    ..The TRF2 complex is primarily involved in telomere protection and contains the TRF2 interacting partner human (h)Rap1 as well as several factors involved in the DNA damage response...
  4. Liu D, O Connor M, Qin J, Songyang Z. Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. J Biol Chem. 2004;279:51338-42 pubmed
    ..They interact with several other telomere regulators including TIN2, PTOP, POT1, and RAP1 to ensure proper maintenance of telomeres. TRF1 and TRF2 are believed to exert distinct functions...
  5. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100-10 pubmed
    ..They are interconnected by three additional shelterin proteins, TIN2, TPP1, and Rap1, forming a complex that allows cells to distinguish telomeres from sites of DNA damage...
  6. O Connor M, Safari A, Xin H, Liu D, Songyang Z. A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. Proc Natl Acad Sci U S A. 2006;103:11874-9 pubmed
    ..of a high-molecular-mass telomeric complex (the mammalian telosome) that contains the six core proteins TRF1, TRF2, RAP1, TIN2, POT1, and TPP1 (formerly named PTOP/PIP1/TINT1) and mediates telomere end-capping and length control...
  7. Martinez P, Thanasoula M, Carlos A, Gomez Lopez G, Tejera A, Schoeftner S, et al. Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites. Nat Cell Biol. 2010;12:768-80 pubmed publisher
    b>Rap1 is a component of the shelterin complex at mammalian telomeres, but its in vivo role in telomere biology has remained largely unknown to date...
  8. de Lange T. How shelterin solves the telomere end-protection problem. Cold Spring Harb Symp Quant Biol. 2010;75:167-77 pubmed publisher
  9. Chen Y, Rai R, Zhou Z, Kanoh J, Ribeyre C, Yang Y, et al. A conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms. Nat Struct Mol Biol. 2011;18:213-21 pubmed publisher
    Repressor activator protein 1 (RAP1) is the most highly conserved telomere protein...
  10. Arat N, Griffith J. Human Rap1 interacts directly with telomeric DNA and regulates TRF2 localization at the telomere. J Biol Chem. 2012;287:41583-94 pubmed publisher
    The TRF2-Rap1 complex suppresses non-homologous end joining and interacts with DNAPK-C to prevent end joining...
  11. Bae N, Baumann P. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol Cell. 2007;26:323-34 pubmed
    ..Biochemical fractionation and reconstitution revealed that telomere protection is mediated by a RAP1/TRF2 complex, providing evidence for a direct role for human RAP1 in the protection of telomeric DNA from NHEJ.
  12. Kabir S, Hockemeyer D, de Lange T. TALEN gene knockouts reveal no requirement for the conserved human shelterin protein Rap1 in telomere protection and length regulation. Cell Rep. 2014;9:1273-80 pubmed publisher
    The conserved protein Rap1 functions at telomeres in fungi, protozoa, and vertebrates. Like yeast Rap1, human Rap1 has been implicated in telomere length regulation and repression of nonhomologous end-joining (NHEJ) at telomeres...
  13. Wang J, Zhang H, Al Shibar M, Willard B, Ray A, Runge K. Rif1 phosphorylation site analysis in telomere length regulation and the response to damaged telomeres. DNA Repair (Amst). 2018;65:26-33 pubmed publisher
    ..protein, negatively regulates telomere length by forming a complex with two other telomere binding proteins, Rap1 and Rif2, to block telomerase recruitment...
  14. Lu J, Vallabhaneni H, Yin J, Liu Y. Deletion of the major peroxiredoxin Tsa1 alters telomere length homeostasis. Aging Cell. 2013;12:635-44 pubmed publisher
    ..Additionally, telomerase-mediated telomere repeat addition is negatively modulated by the levels of telomere-bound Rap1-Rif1-Rif2 protein complex...
  15. Yue X, Acun A, Zorlutuna P. Transcriptome profiling of 3D co-cultured cardiomyocytes and endothelial cells under oxidative stress using a photocrosslinkable hydrogel system. Acta Biomater. 2017;58:337-348 pubmed publisher
    ..oxidative phosphorylation pathway and activating pathways such as the drug metabolism-cytochrome P450 pathway, Rap1 signaling pathway, and adrenergic signaling in cardiomyocytes pathway...
  16. Rho S, Ando K, Fukuhara S. Dynamic Regulation of Vascular Permeability by Vascular Endothelial Cadherin-Mediated Endothelial Cell-Cell Junctions. J Nippon Med Sch. 2017;84:148-159 pubmed publisher
    ..Furthermore, reorganization of the actomyosin cytoskeleton by Rap1, a small GTPase that belongs to the Ras subfamily, and Rho family small GTPases, regulates VE-cadherin-mediated ..
  17. Zhou Y, Cheng C, Baranenko D, Wang J, Li Y, Lu W. Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics. Int J Mol Sci. 2018;19: pubmed publisher
    ..action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1) ..
  18. Pisitkun T, Bieniek J, Tchapyjnikov D, Wang G, Wu W, Shen R, et al. High-throughput identification of IMCD proteins using LC-MS/MS. Physiol Genomics. 2006;25:263-76 pubmed
    ..syntaxin-7, Rap1, GAPDH, heat shock protein (HSP)70, and cathepsin D...
  19. Adamczyk J, Deregowska A, Skoneczny M, Skoneczna A, Kwiatkowska A, Potocki L, et al. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts. Oncotarget. 2016;7:29958-76 pubmed publisher
    ..by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages...
  20. Xia J, Guo Z, Yang Z, Zhu X, Kang S, Yang X, et al. Proteomics-based identification of midgut proteins correlated with Cry1Ac resistance in Plutella xylostella (L.). Pestic Biochem Physiol. 2016;132:108-17 pubmed publisher
    ..solute carrier family 36 member 1 (SLC36A1), NADH dehydrogenase iron-sulfur protein 3 (NDUFS3), prohibitin and Rap1 GTPase-activating protein 1...
  21. Kasirer Friede A, Kang J, Kahner B, Ye F, Ginsberg M, Shattil S. ADAP interactions with talin and kindlin promote platelet integrin αIIbβ3 activation and stable fibrinogen binding. Blood. 2014;123:3156-65 pubmed publisher
    ..In T lymphocytes, SKAP1 is the ADAP-associated molecule that activates integrins through direct linkages with Rap1 effectors (regulator of cell adhesion and polarization enriched in lymphoid tissues; Rap1-interacting adapter ..
  22. Ma X, Shen M, Hu B, Wang B, Yang W, Lv L, et al. CD73 promotes hepatocellular carcinoma progression and metastasis via activating PI3K/AKT signaling by inducing Rap1-mediated membrane localization of P110β and predicts poor prognosis. J Hematol Oncol. 2019;12:37 pubmed publisher
    ..Mechanistically, adenosine produced by CD73 binds to adenosine A2A receptor (A2AR) and activates Rap1, which recruits P110β to the plasma membrane and triggers PIP3 production, thereby promoting AKT phosphorylation ..
  23. De Las Peñas A, Juárez Cepeda J, López Fuentes E, Briones Martín Del Campo M, Gutiérrez Escobedo G, Castaño I. Local and regional chromatin silencing in Candida glabrata: consequences for adhesion and the response to stress. FEMS Yeast Res. 2015;15: pubmed publisher
    ..Sir2 can associate with Sir4, which is then recruited to the telomere by Rap1 and yKu...
  24. Parker W, Rhea E, Qu Z, Hecker M, May J. Intracellular ascorbate tightens the endothelial permeability barrier through Epac1 and the tubulin cytoskeleton. Am J Physiol Cell Physiol. 2016;311:C652-C662 pubmed publisher
    ..Although Epac1 was required, its mediator Rap1 was not activated...
  25. Zhu Y, Mei F, Luo P, Cheng X. A cell-based, quantitative and isoform-specific assay for exchange proteins directly activated by cAMP. Sci Rep. 2017;7:6200 pubmed publisher
    ..medium to high throughput screening assay that is capable of monitoring EPAC-mediated activation of cellular Rap1 in an isoform-specific manner is described...
  26. Walther R, Burki M, Pinal N, Rogerson C, Pichaud F. Rap1, Canoe and Mbt cooperate with Bazooka to promote zonula adherens assembly in the fly photoreceptor. J Cell Sci. 2018;131: pubmed publisher
    ..Here, we show that the small GTPase Rap1, its effector Canoe (Cno) and the Cdc42 effector kinase Mushroom bodies tiny (Mbt), converge in regulating ..
  27. Loregian A, Bortolozzo K, Boso S, Caputo A, Palu G. Interaction of Sp1 transcription factor with HIV-1 Tat protein: looking for cellular partners. FEBS Lett. 2003;543:61-5 pubmed
  28. Shah B, Lutter D, Tsytsyura Y, Glyvuk N, Sakakibara A, Klingauf J, et al. Rap1 GTPases Are Master Regulators of Neural Cell Polarity in the Developing Neocortex. Cereb Cortex. 2017;27:1253-1269 pubmed publisher
    ..Here, we show that Rap1 GTPases perform essential functions for cortical organization as master regulators of cell polarity...
  29. Zhang X, Huang X, Fang C, Li Q, Cui J, Sun J, et al. miR-124 Regulates the Expression of BACE1 in the Hippocampus Under Chronic Cerebral Hypoperfusion. Mol Neurobiol. 2017;54:2498-2506 pubmed publisher
    ..Thus, miR-124 was the key factor in this hypoxia/A?-miR-124-BACE1-A? cycle. The activation of EPAC-Rap1 pathway was involved in the inhibition of miR-124 in hippocampus under hypoxia or A? insult...
  30. Boulaftali Y, Owens A, Beale A, Piatt R, Casari C, Lee R, et al. CalDAG-GEFI Deficiency Reduces Atherosclerotic Lesion Development in Mice. Arterioscler Thromb Vasc Biol. 2016;36:792-9 pubmed publisher
    ..work identified 2 independent, yet synergistic, signaling pathways that lead to the activation of the small GTPase Rap1; one mediated by the guanine nucleotide exchange factor, CalDAG-GEFI (CDGI), the other by P2Y12, a platelet ..
  31. Lackner D, Durocher D, Karlseder J. A siRNA-based screen for genes involved in chromosome end protection. PLoS ONE. 2011;6:e21407 pubmed publisher
    ..The telomeric core complex is called shelterin and is comprised of the proteins TRF1, TRF2, POT1, TIN2, TPP1 and RAP1. Excessive telomere shortening or de-protection of telomeres through the loss of shelterin subunits allows the ..
  32. Wittchen E, Nishimura E, McCloskey M, Wang H, Quilliam L, Chrzanowska Wodnicka M, et al. Rap1 GTPase activation and barrier enhancement in rpe inhibits choroidal neovascularization in vivo. PLoS ONE. 2013;8:e73070 pubmed publisher
    ..b>Rap1 GTPase is involved in regulating both endothelial and epithelial cell junctions; the specific role of Rap1A vs...
  33. Yarwood S, Parnell E, Bird R. The cyclic AMP phosphodiesterase 4D5 (PDE4D5)/receptor for activated C-kinase 1 (RACK1) signalling complex as a sensor of the extracellular nano-environment. Cell Signal. 2017;35:282-289 pubmed publisher
    ..This supports PDE4D5 and RACK1 as potential regulators of cell adhesion, spreading and migration through the non-classical exchange protein activated by cyclic AMP (EPAC1)/Rap1 signalling route.
  34. Liu H, Lo C, Yeung O, Li C, Liu X, Qi X, et al. NLRP3 inflammasome induced liver graft injury through activation of telomere-independent RAP1/KC axis. J Pathol. 2017;242:284-296 pubmed publisher
    ..led us to focus on one of the associated upstream regulators, telomere-independent repressor activator protein 1 (RAP1), which was further proved to be co-localized with NLRP3 in neutrophils...
  35. Schmidt A, Lv Z, Großhans J. ELMO and Sponge specify subapical restriction of Canoe and formation of the subapical domain in early Drosophila embryos. Development. 2018;145: pubmed publisher
    Canoe/Afadin and the GTPase Rap1 specify the subapical domain during cellularization in Drosophila embryos. The timing of domain formation is unclear...
  36. Xu Y, Chen X, Lin L, Chen H, Yu S, Li D. MicroRNA-149 is associated with clinical outcome in human neuroblastoma and modulates cancer cell proliferation through Rap1 independent of MYCN amplification. Biochimie. 2017;139:1-8 pubmed publisher
    ..Possible downstream target of miR-149, Ras-related protein 1 (Rap1), was evaluated by qRT-PCR and western blot in lentiviral-transduced NB cells...
  37. Molina Ortiz P, Orban T, Martin M, Habets A, Dequiedt F, Schurmans S. Rasa3 controls turnover of endothelial cell adhesion and vascular lumen integrity by a Rap1-dependent mechanism. PLoS Genet. 2018;14:e1007195 pubmed publisher
    Rasa3 is a GTPase activating protein of the GAP1 family which targets R-Ras and Rap1. Although catalytic inactivation or deletion of Rasa3 in mice leads to severe hemorrhages and embryonic lethality, the biological function and cellular ..
  38. Mukherjee J, Johannessen T, Ohba S, Chow T, Jones L, Pandita A, et al. Mutant IDH1 Cooperates with ATRX Loss to Drive the Alternative Lengthening of Telomere Phenotype in Glioma. Cancer Res. 2018;78:2966-2977 pubmed publisher
    ..The telomere capping complex component RAP1 and the nonhomologous DNA end joining repair factor XRCC1 were each downregulated consistently in these tumorigenic ..
  39. Seino S, Takahashi H, Takahashi T, Shibasaki T. Treating diabetes today: a matter of selectivity of sulphonylureas. Diabetes Obes Metab. 2012;14 Suppl 1:9-13 pubmed publisher
    ..SUs are now known also to activate cAMP sensor Epac2 (cAMP-GEFII) to Rap1 signalling, which promotes insulin granule exocytosis...
  40. Dusaban S, Kunkel M, Smrcka A, Brown J. Thrombin promotes sustained signaling and inflammatory gene expression through the CDC25 and Ras-associating domains of phospholipase Cϵ. J Biol Chem. 2015;290:26776-83 pubmed publisher
    ..We hypothesized that the ability of PLCϵ to function as a guanine nucleotide exchange factor (GEF) for Rap1 supports sustained downstream signaling via feedback of Rap1 to the enzyme Ras-associating (RA2) domain...
  41. Margraf A, Nussbaum C, Rohwedder I, Klapproth S, Kurz A, Florian A, et al. Maturation of Platelet Function During Murine Fetal Development In Vivo. Arterioscler Thromb Vasc Biol. 2017;37:1076-1086 pubmed publisher
    ..Interestingly, we also measured reduced levels of the integrin-activating proteins Kindlin-3, Talin-1, and Rap1 during fetal development...
  42. Berrou E, Adam F, Lebret M, Planche V, Fergelot P, Issertial O, et al. Gain-of-Function Mutation in Filamin A Potentiates Platelet Integrin ?IIb?3 Activation. Arterioscler Thromb Vasc Biol. 2017;37:1087-1097 pubmed publisher
    ..integrin activation and a parallel increase in talin recruitment to ?3, contrasting with normal Rap1 activation...
  43. Onodera Y, Nam J, Bissell M. Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. J Clin Invest. 2014;124:367-84 pubmed publisher
    ..Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification ..
  44. Kamei Y, Tai A, Dakeyama S, Yamamoto K, Inoue Y, Kishimoto Y, et al. Transcription factor genes essential for cell proliferation and replicative lifespan in budding yeast. Biochem Biophys Res Commun. 2015;463:351-6 pubmed publisher
    ..Heterozygous diploid knockout strains for FHL1, RAP1, REB1, and MCM1 genes showed significantly short lifespan...
  45. Nagai T, Nakamuta S, Kuroda K, Nakauchi S, Nishioka T, Takano T, et al. Phosphoproteomics of the Dopamine Pathway Enables Discovery of Rap1 Activation as a Reward Signal In Vivo. Neuron. 2016;89:550-65 pubmed publisher
    ..known and novel PKA substrates downstream of the D1R and obtained more than 100 candidate substrates, including Rap1 GEF (Rasgrp2)...
  46. Maeta K, Edamatsu H, Nishihara K, Ikutomo J, Bilasy S, Kataoka T. Crucial Role of Rapgef2 and Rapgef6, a Family of Guanine Nucleotide Exchange Factors for Rap1 Small GTPase, in Formation of Apical Surface Adherens Junctions and Neural Progenitor Development in the Mouse Cerebral Cortex. Eneuro. 2016;3: pubmed publisher
    ..Rapgef2 and Rapgef6 constitute a unique family of guanine nucleotide exchange factors for Rap1 small GTPase, which is known to play crucial roles in migration of postmitotic neurons...
  47. Chawla R, Redon S, Raftopoulou C, Wischnewski H, Gagos S, Azzalin C. Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication. EMBO J. 2011;30:4047-58 pubmed publisher
    ..Our results portray a scenario where UPF1 orchestrates crucial aspects of telomere biology, including telomere replication and telomere length homeostasis...
  48. Lezoualc h F, Fazal L, Laudette M, Conte C. Cyclic AMP Sensor EPAC Proteins and Their Role in Cardiovascular Function and Disease. Circ Res. 2016;118:881-97 pubmed publisher
    ..The 2 EPAC isoforms, EPAC1 and EPAC2, are guanine-nucleotide exchange factors for the Ras-like GTPases, Rap1 and Rap2, which they activate independently of the classical effector of cAMP, protein kinase A...
  49. Yang D, Roh S, Jeong S. The axon guidance function of Rap1 small GTPase is independent of PlexA RasGAP activity in Drosophila. Dev Biol. 2016;418:258-67 pubmed publisher
    ..Here, we found that Drosophila Rap1, a member of the Ras family of GTPases, plays an important role controlling intersegmental nerve b motor axon ..
  50. Larcher M, Pasquier E, MacDonald R, Wellinger R. Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends. PLoS Genet. 2016;12:e1006479 pubmed publisher
    ..After repair, the yKu-distal portion of telomeres is bound by Rap1, which in turn reduces the potential for yKu to mediate NHEJ...
  51. Yang Y, Ye C, Wang L, An G, Tian Z, Meng L, et al. Repressor activator protein 1-promoted colorectal cell migration is associated with the regulation of Vimentin. Tumour Biol. 2017;39:1010428317695034 pubmed publisher
    ..Thus, our study suggests that repressor activator protein 1 is a prognostic marker and a potential target for colorectal cancer therapy. ..
  52. van Hooren K, van Agtmaal E, Fernandez Borja M, van Mourik J, Voorberg J, Bierings R. The Epac-Rap1 signaling pathway controls cAMP-mediated exocytosis of Weibel-Palade bodies in endothelial cells. J Biol Chem. 2012;287:24713-20 pubmed publisher
    ..of WPB exocytosis, namely the guanine nucleotide exchange factor Epac1 and its substrate, the small GTPase Rap1. Epinephrine stimulation of endothelial cells leads to Rap1 activation in a PKA-independent fashion...
  53. Yeung J, Tourdot B, Adili R, Green A, Freedman C, Fernandez Perez P, et al. 12(S)-HETrE, a 12-Lipoxygenase Oxylipin of Dihomo-?-Linolenic Acid, Inhibits Thrombosis via G?s Signaling in Platelets. Arterioscler Thromb Vasc Biol. 2016;36:2068-77 pubmed publisher
    ..DGLA inhibited ex vivo platelet aggregation and Rap1 activation in wild-type mice, but not in mice lacking 12-LOX expression (12-LOX(-/-))...
  54. Choi K, Farrell A, Lakamp A, Ouellette M. Characterization of the DNA binding specificity of Shelterin complexes. Nucleic Acids Res. 2011;39:9206-23 pubmed publisher
    ..In its most abundant form, the complex is composed of six core components: TRF1, TRF2, POT1, TIN2, TPP1 and RAP1. Of these subunits, three can interact directly with either single-stranded (POT1) or double-stranded (TRF1, TRF2) ..
  55. Jirapattharasate C, Adjou Moumouni P, Cao S, Iguchi A, Liu M, Wang G, et al. Molecular epidemiology of bovine Babesia spp. and Theileria orientalis parasites in beef cattle from northern and northeastern Thailand. Parasitol Int. 2016;65:62-69 pubmed publisher
    ..0% of the samples. Sequencing analysis revealed that B. bigemina RAP1 gene and B. bovis SBP2 gene were conserved among the parasites from different cattle samples...
  56. Natarajan S, Begum F, Gim J, Wark L, Henderson D, Davie J, et al. High Mobility Group A2 protects cancer cells against telomere dysfunction. Oncotarget. 2016;7:12761-82 pubmed publisher
    ..This interaction was independent of HMGA2 DNA-binding and did not require the TRF2 interacting partner RAP1 but involved the homodimerization and hinge regions of TRF2...
  57. Li B, de Lange T. Rap1 affects the length and heterogeneity of human telomeres. Mol Biol Cell. 2003;14:5060-8 pubmed
    ..Because the human Rap1 ortholog hRap1 does not bind to telomeric DNA directly but is recruited to telomeres by TRF2, we examined its role ..
  58. Lim J, Juhnn Y. Isoproterenol increases histone deacetylase 6 expression and cell migration by inhibiting ERK signaling via PKA and Epac pathways in human lung cancer cells. Exp Mol Med. 2016;48:e204 pubmed publisher
    ..ISO activated Rap1 via Epac, and constitutively active Rap1A increased the HDAC6 level; however, the knockdown of Rap1A decreased the ..
  59. Wang W, Chen J, Luo L, Li Y, Liu J, Zhang W. Effect of cadmium on kitl pre-mRNA alternative splicing in murine ovarian granulosa cells and its associated regulation by miRNAs. J Appl Toxicol. 2018;38:227-239 pubmed publisher
    ..that the target genes of the differentially expressed miRNAs were mainly enriched in the Ras signaling pathway, the Rap1 signaling pathway, the Foxo signaling pathway, the Hippo signaling pathway, the MAPK signaling pathway and the ..
  60. Umezawa Y, Akiyama H, Okada K, Ishida S, Nogami A, Oshikawa G, et al. Molecular mechanisms for enhancement of stromal cell-derived factor 1-induced chemotaxis by platelet endothelial cell adhesion molecule 1 (PECAM-1). J Biol Chem. 2017;292:19639-19655 pubmed publisher
    ..respectively, SDF-1-induced G?i-dependent activation of the PI3K/Akt/mTORC1 pathway and small GTPase Rap1 in hematopoietic 32Dcl3 cells, and these changes in activation correlated with chemotaxis...
  61. Da Silva N, Arasaradnam R, Getliffe K, Sung E, Oo Y, Nwokolo C. Altered mRNA expression of telomere binding proteins (TPP1, POT1, RAP1, TRF1 and TRF2) in ulcerative colitis and Crohn's disease. Dig Liver Dis. 2010;42:544-8 pubmed publisher
    ..TPP1, POT1, RAP1, TRF1 and TRF2 mRNA expression in PBMC and activated T lymphocytes was measured with RT-PCR...
  62. Raab M, Smith X, Matthess Y, Strebhardt K, Rudd C. SKAP1 protein PH domain determines RapL membrane localization and Rap1 protein complex formation for T cell receptor (TCR) activation of LFA-1. J Biol Chem. 2011;286:29663-70 pubmed publisher
    ..SKAP1 (SKAP-55) is the upstream regulator needed for TCR-induced RapL-Rap1 complex formation and LFA-1 activation...
  63. Biancucci M, Rabideau A, Lu Z, Loftis A, Pentelute B, Satchell K. Substrate Recognition of MARTX Ras/Rap1-Specific Endopeptidase. Biochemistry. 2017;56:2747-2757 pubmed publisher
    Ras/Rap1-specific endopeptidase (RRSP) is a cytotoxic effector domain of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin of highly virulent strains of Vibrio vulnificus...
  64. Vitali E, Boemi I, Rosso L, Cambiaghi V, Novellis P, Mantovani G, et al. FLNA is implicated in pulmonary neuroendocrine tumors aggressiveness and progression. Oncotarget. 2017;8:77330-77340 pubmed publisher
    ..and migration in PNT cell line (H727 cells) and primary cultures and the possible interaction between FLNA and Rap1-GTPase. FLNA is highly expressed in PNTs with high malignant grade...
  65. Noda K, Zhang J, Fukuhara S, Kunimoto S, Yoshimura M, Mochizuki N. Vascular endothelial-cadherin stabilizes at cell-cell junctions by anchoring to circumferential actin bundles through alpha- and beta-catenins in cyclic AMP-Epac-Rap1 signal-activated endothelial cells. Mol Biol Cell. 2010;21:584-96 pubmed publisher
    ..Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin-dependent cell adhesion...
  66. Gaullier G, Miron S, Pisano S, Buisson R, Le Bihan Y, Tellier Lebègue C, et al. A higher-order entity formed by the flexible assembly of RAP1 with TRF2. Nucleic Acids Res. 2016;44:1962-76 pubmed publisher
    ..Within shelterin, RAP1 is recruited through its interaction with TRF2, and TRF2 is required for telomere protection through a network of ..
  67. Takahashi M, Li Y, Dillon T, Stork P. Phosphorylation of Rap1 by cAMP-dependent Protein Kinase (PKA) Creates a Binding Site for KSR to Sustain ERK Activation by cAMP. J Biol Chem. 2017;292:1449-1461 pubmed publisher
    ..Two small G proteins, Ras and Rap1 have been proposed to mediate this activation...
  68. Necasova I, Janoušková E, Klumpler T, Hofr C. Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1 restores it. Nucleic Acids Res. 2017;45:12170-12180 pubmed publisher
    ..Repressor activator protein 1 (Rap1) binds TRF2 and improves telomeric DNA recognition...
  69. Garcon F, Okkenhaug K. PI3K? promotes CD4(+) T-cell interactions with antigen-presenting cells by increasing LFA-1 binding to ICAM-1. Immunol Cell Biol. 2016;94:486-95 pubmed publisher
    ..Here we show that in T cells, PI3K? attenuates the activation of Rac1, but sustains the activation of Rap1. Consequently, PI3K? increases LFA-1-dependent adhesion to form stable conjugates with APCs...
  70. Battram A, Durrant T, Agbani E, Heesom K, Paul D, Piatt R, et al. The Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) Binder Rasa3 Regulates Phosphoinositide 3-kinase (PI3K)-dependent Integrin αIIbβ3 Outside-in Signaling. J Biol Chem. 2017;292:1691-1704 pubmed publisher
    ..Expression of wild-type Rasa3 in integrin αIIbβ3-expressing CHO cells blocked Rap1 activity and integrin αIIbβ3-mediated spreading on fibrinogen...
  71. Yang Y, Zhang J, Yan Y, Cai H, Li M, Sun K, et al. Low expression of Rap1GAP is associated with epithelial-mesenchymal transition (EMT) and poor prognosis in gastric cancer. Oncotarget. 2017;8:8057-8068 pubmed publisher
    ..These results suggest that Rap1GAP functions as a novel suppressor of EMT and tumor metastasis in GC, and loss of Rap1GAP predicts poor prognosis in GC. ..
  72. Mittal N, Guimaraes J, Gross T, Schmidt A, Vina Vilaseca A, Nedialkova D, et al. The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan. Nat Commun. 2017;8:457 pubmed publisher
    ..The promoters of repressed genes contain Rap1 binding motifs...
  73. Roy K, Chanfreau G. A global function for transcription factors in assisting RNA polymerase II termination. Transcription. 2017;:1-6 pubmed publisher
    ..Here, we propose that a subset of TFs such as Reb1, Abf1, Rap1, and TFIIIB also serve a major function in partitioning transcription units by assisting the Nrd1p-Nab3p-Sen1p Pol ..
  74. Zha Y, Gan P, Yao Q, Ran F, Tan J. Downregulation of Rap1 promotes 5-fluorouracil-induced apoptosis in hepatocellular carcinoma cell line HepG2. Oncol Rep. 2014;31:1691-8 pubmed publisher
    Recent studies have revealed that repressor/activator protein (Rap1) not only protects telomeres from sister chromatid exchange, but also functions in genomewide transcriptional regulation...
  75. Harari Y, Kupiec M. Mec1ATR is needed for extensive telomere elongation in response to ethanol in yeast. Curr Genet. 2018;64:223-234 pubmed publisher
    ..In particular, exposure to ethanol induces an extensive telomere elongation response due to a reduction in RAP1 mRNA and protein levels...
  76. Zhang Y, Chen Y, Xu Q, Liu R, Wu N, Chen G. Identification of DNA methylation and transcriptional regulatory regions in the promoter of duck retinoic acid inducible gene I (RIG-I). Br Poult Sci. 2017;:1-5 pubmed publisher
    ..region was identified, localised between -301 and ~+14 bp, where multiple transcription factor binding sites including IRF1, RXR?, AP-2?A, RAP1, NF-1 and SP1 motifs were identified that significantly enhanced RIG-I promoter activity.
  77. Che Y, Luo S, Li G, Cheng M, Gao Y, Li X, et al. The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis. Cancer Lett. 2015;359:241-9 pubmed publisher
    ..To evaluate the contribution of C3G to Rap1 activity, 36 patients with serous ovarian cancer (SOC) were investigated...
  78. Menendez J, Rubio M, Campisi J, Lupu R. Heregulin, a new regulator of telomere length in human cells. Oncotarget. 2015;6:39422-36 pubmed publisher
    ..nucleoplasmic staining pattern of endogenous HRGβ2 appeared to co-localize with TRF2 and, concomitantly with RAP1, a telomere regulator that specifically interacts with TRF2...
  79. Cai Y, Sukhova G, Wong H, Xu A, Tergaonkar V, Vanhoutte P, et al. Rap1 induces cytokine production in pro-inflammatory macrophages through NFκB signaling and is highly expressed in human atherosclerotic lesions. Cell Cycle. 2015;14:3580-92 pubmed publisher
    Repressor activator protein 1 (Rap1) is essential for maintaining telomere length and structural integrity, but it also exerts other non-telomeric functions...
  80. Li C, Lo C, Lian Q, Ng K, Liu X, Ma Y, et al. Repressor and activator protein accelerates hepatic ischemia reperfusion injury by promoting neutrophil inflammatory response. Oncotarget. 2016;7:27711-23 pubmed publisher
    Repressor and activator protein (Rap1) directly regulates nuclear factor-?B (NF-?B) dependent signaling, which contributes to hepatic IRI...
  81. Lim C, Zaug A, Kim H, Cech T. Reconstitution of human shelterin complexes reveals unexpected stoichiometry and dual pathways to enhance telomerase processivity. Nat Commun. 2017;8:1075 pubmed publisher
    ..TRF2 interacts with TIN2 with an unexpected 2:1 stoichiometry in the context of shelterin (RAP12:TRF22:TIN21:TPP11:POT11)...
  82. Kim J, Liu J, Hu X, Yu C, Roskamp K, Sankaran B, et al. Structural Basis for Shelterin Bridge Assembly. Mol Cell. 2017;68:698-714.e5 pubmed publisher
    ..sequence-specific double- and single-stranded DNA-binding proteins, Taz1 and Pot1, respectively, bridged by Rap1, Poz1, and Tpz1...
  83. Jeong Y, Her J, Chung I. NEDD8 ultimate buster-1 regulates the abundance of TRF1 at telomeres by promoting its proteasomal degradation. FEBS Lett. 2016;590:1776-90 pubmed publisher
    ..These data suggest that NUB1 participates in telomere maintenance by regulating the levels of TRF1 at telomeres through both NEDD8-dependent and NEDD8-independent pathways. ..
  84. Li Y, Dillon T, Takahashi M, Earley K, Stork P. Protein Kinase A-independent Ras Protein Activation Cooperates with Rap1 Protein to Mediate Activation of the Extracellular Signal-regulated Kinases (ERK) by cAMP. J Biol Chem. 2016;291:21584-21595 pubmed
    ..Two small G proteins, Ras and Rap1, have been proposed to mediate this activation, with either Ras or Rap1 acting in distinct cell types...
  85. Xiong Y, Ye C, Yang N, Li M, Liu H. Ubc9 Binds to ADAP and Is Required for Rap1 Membrane Recruitment, Rac1 Activation, and Integrin-Mediated T Cell Adhesion. J Immunol. 2017;199:4142-4154 pubmed publisher
    ..as an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL and for activation of the small GTPase Rac1 in T cell adhesion...
  86. Choi J, Kang H, Jang J, Choi Y, Kim M, Kim J, et al. Polymorphisms in telomere maintenance genes and risk of lung cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:2773-81 pubmed publisher
    ..evaluate the associations between polymorphisms in telomere maintenance genes (TERT, TRF1, TNKS1, TRF2, RAP1, and POT1) and lung cancer risk...
  87. Zee R, Ridker P, Chasman D. Genetic variants in eleven telomere-associated genes and the risk of incident cardio/cerebrovascular disease: The Women's Genome Health Study. Clin Chim Acta. 2011;412:199-202 pubmed publisher
    ..tSNPs) of 11 telomere-associated candidate genes (TERT, POT1, TNKS, TERF1, TNKS2, UCP2, TEP1, ACD, TERF2, TERF2IP, and TERC) were investigated in 23,294 Caucasian participants of the Women's Genome Health Study...
  88. Kusama K, Yoshie M, Tamura K, Kodaka Y, Hirata A, Sakurai T, et al. Regulation of decidualization in human endometrial stromal cells through exchange protein directly activated by cyclic AMP (Epac). Placenta. 2013;34:212-21 pubmed publisher
    ..The present study was undertaken to examine the involvement of a mediator of cAMP signaling, exchange protein directly activated by cAMP (Epac), in decidualization of cultured ESCs...
  89. Zhan S, Zhao W, Song T, Dong Y, Guo J, Cao J, et al. Dynamic transcriptomic analysis in hircine longissimus dorsi muscle from fetal to neonatal development stages. Funct Integr Genomics. 2018;18:43-54 pubmed publisher
    ..that DEGs from class I profiles were significantly enriched in 22 pathways and the most enriched pathway was Rap1 signaling pathway...
  90. Lian S, Meng L, Yang Y, Ma T, Xing X, Feng Q, et al. PRL-3 promotes telomere deprotection and chromosomal instability. Nucleic Acids Res. 2017;45:6546-6571 pubmed publisher
    ..We report here that shelterin component RAP1 mediates association between PRL-3 and TRF2...
  91. Inaba H, Yoda K, Adachi H. The F-actin-binding RapGEF GflB is required for efficient macropinocytosis in Dictyostelium. J Cell Sci. 2017;130:3158-3172 pubmed publisher
    ..The Dictyostelium discoideum protein GflB is a guanine nucleotide exchange factor (GEF) of Rap1, and is involved in chemotaxis. Here, we studied the role of GflB in macropinocytosis, phagocytosis and cytokinesis...
  92. Zhu L, Yang J, Bromberger T, Holly A, Lu F, Liu H, et al. Structure of Rap1b bound to talin reveals a pathway for triggering integrin activation. Nat Commun. 2017;8:1744 pubmed publisher
    ..Membrane-anchored mammalian small GTPase Rap1 is known to bind talin-F0 domain but the binding was shown to be weak and thus hardly studied...