phosphatidylethanolamine binding protein


Summary: A ubiquitously found basic protein that binds to phosphatidylethanolamine and NUCLEOTIDES. It is an endogenous inhibitor of RAF KINASES and may play a role in regulating SIGNAL TRANSDUCTION. Phosphatidylethanolamine-binding protein is the precursor of hippocampal cholinergic neurostimulating peptide, which is cleaved from the N-terminal region of the protein.

Top Publications

  1. Sagisaka T, Matsukawa N, Toyoda T, Uematsu N, Kanamori T, Wake H, et al. Directed neural lineage differentiation of adult hippocampal progenitor cells via modulation of hippocampal cholinergic neurostimulating peptide precursor expression. Brain Res. 2010;1327:107-17 pubmed publisher
  2. Minoo P, Zlobec I, Baker K, Tornillo L, Terracciano L, Jass J, et al. Loss of raf-1 kinase inhibitor protein expression is associated with tumor progression and metastasis in colorectal cancer. Am J Clin Pathol. 2007;127:820-7 pubmed
    ..Methylation analysis of 28 cases showed that loss of RKIP expression is unlikely to be due to promoter methylation.Loss of RKIP expression is a marker of tumor progression and distant metastasis in MMR-proficient and MMR-deficient CRCs. ..
  3. Moen E, Wen S, Anwar T, Cross Knorr S, Brilliant K, Birnbaum F, et al. Regulation of RKIP function by Helicobacter pylori in gastric cancer. PLoS ONE. 2012;7:e37819 pubmed publisher
    ..In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells. ..
  4. Simister P, Banfield M, Brady R. The crystal structure of PEBP-2, a homologue of the PEBP/RKIP family. Acta Crystallogr D Biol Crystallogr. 2002;58:1077-80 pubmed
    ..Nonetheless, mPEBP-2 is seen to be very similar in structure to other PEBP proteins from human, bovine and plant sources. Regions of distinctive sequence associated with the PEBP-2 subset are discussed with reference to this structure. ..
  5. Yi C, Peng Y, Guo C, Lin D. 1H, 13C, 15N backbone and side-chain resonance assignments of the human Raf-1 kinase inhibitor protein. Biomol NMR Assign. 2011;5:63-6 pubmed publisher
    ..Raf-1 kinase inhibitor protein (RKIP) plays a pivotal role in modulating multiple signaling networks. Here we report backbone and side chain resonance assignments of uniformly (15)N, (13)C labeled human RKIP. ..
  6. Baritaki S, Katsman A, Chatterjee D, Yeung K, Spandidos D, Bonavida B. Regulation of tumor cell sensitivity to TRAIL-induced apoptosis by the metastatic suppressor Raf kinase inhibitor protein via Yin Yang 1 inhibition and death receptor 5 up-regulation. J Immunol. 2007;179:5441-53 pubmed
    ..We suggest that RKIP may serve as an immune surveillance cancer gene, and its low expression or absence in tumors allows the tumor to escape host immune cytotoxic effector cells. ..
  7. Michaels S, Himelblau E, Kim S, Schomburg F, Amasino R. Integration of flowering signals in winter-annual Arabidopsis. Plant Physiol. 2005;137:149-56 pubmed
    ..Thus, the integration of flowering signals from the photoperiod and vernalization pathways occurs, at least in part, through the regulation of FT, TSF, and SOC1. ..
  8. Yun J, Frankenberger C, Kuo W, Boelens M, Eves E, Cheng N, et al. Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer. EMBO J. 2011;30:4500-14 pubmed publisher
  9. Baritaki S, Yeung K, Palladino M, Berenson J, Bonavida B. Pivotal roles of snail inhibition and RKIP induction by the proteasome inhibitor NPI-0052 in tumor cell chemoimmunosensitization. Cancer Res. 2009;69:8376-85 pubmed publisher
    ..The findings also identified Snail and RKIP as targets for reversal of resistance. ..

More Information


  1. Park S, Yeung M, Beach S, Shields J, Yeung K. RKIP downregulates B-Raf kinase activity in melanoma cancer cells. Oncogene. 2005;24:3535-40 pubmed
    ..The low expression of RKIP and its antagonistic action on B-Raf suggests that RKIP may play an important role in melanoma turmorgenesis. ..
  2. Banfield M, Brady R. The structure of Antirrhinum centroradialis protein (CEN) suggests a role as a kinase regulator. J Mol Biol. 2000;297:1159-70 pubmed
  3. Al Mulla F, Bitar M, Taqi Z, Rath O, Kolch W. RAF kinase inhibitory protein (RKIP) modulates cell cycle kinetics and motility. Mol Biosyst. 2011;7:928-41 pubmed publisher
  4. Serre L, Pereira de Jesus K, Zelwer C, Bureaud N, Schoentgen F, Benedetti H. Crystal structures of YBHB and YBCL from Escherichia coli, two bacterial homologues to a Raf kinase inhibitor protein. J Mol Biol. 2001;310:617-34 pubmed
    ..This structural variety should correspond to the recognition of multiple cellular partners. ..
  5. Kroslak T, Koch T, Kahl E, Hollt V. Human phosphatidylethanolamine-binding protein facilitates heterotrimeric G protein-dependent signaling. J Biol Chem. 2001;276:39772-8 pubmed
    ..These data suggest a novel function of hPBP in regulating G protein and G protein-coupled receptor signaling in vivo. ..
  6. Dabbous M, Jefferson M, Haney L, Thomas E. Biomarkers of metastatic potential in cultured adenocarcinoma clones. Clin Exp Metastasis. 2011;28:101-11 pubmed publisher
    ..Proteins that are positively correlated with metastatic potential may prove more useful as clinical biomarkers, but those with negative correlations may still provide useful information about underlying mechanisms of metastatic spread. ..
  7. Klysik J, Theroux S, Sedivy J, Moffit J, Boekelheide K. Signaling crossroads: the function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction. Cell Signal. 2008;20:1-9 pubmed
    ..In this review, the role of RKIP-1 in cellular signaling, and especially its functions revealed using a mouse knockout model, are discussed. ..
  8. Al Mulla F, Hagan S, Al Ali W, Jacob S, Behbehani A, Bitar M, et al. Raf kinase inhibitor protein: mechanism of loss of expression and association with genomic instability. J Clin Pathol. 2008;61:524-9 pubmed publisher
    ..RKIP loss by hypermethylation of its promoter could have a significant influence on colorectal cancer aneuploidy, which might explain its association with metastatic progression. ..
  9. Wang J, Yang Y, Wang A, Yao B, Xie G, Feng G, et al. Immunohistochemical detection of the Raf kinase inhibitor protein in nonneoplastic gastric tissue and gastric cancer tissue. Med Oncol. 2010;27:219-23 pubmed publisher
    ..Our data suggest that RKIP may play a role in the genesis and metastasis of gastric cancer. ..
  10. Zeng L, Imamoto A, Rosner M. Raf kinase inhibitory protein (RKIP): a physiological regulator and future therapeutic target. Expert Opin Ther Targets. 2008;12:1275-87 pubmed
    Raf kinase inhibitory protein (RKIP) belongs to the phosphatidylethanolamine binding protein (PEBP) family that is expressed in both prokaryotic and euakaryotic organisms...
  11. Trakul N, Menard R, Schade G, Qian Z, Rosner M. Raf kinase inhibitory protein regulates Raf-1 but not B-Raf kinase activation. J Biol Chem. 2005;280:24931-40 pubmed
    ..These results indicate that selective modulation of c-Raf-1 but not B-Raf activation by RKIP can limit the dynamic range of the MAPK signaling response to growth factors and may play a critical role in growth and development. ..
  12. Schuierer M, Bataille F, Hagan S, Kolch W, Bosserhoff A. Reduction in Raf kinase inhibitor protein expression is associated with increased Ras-extracellular signal-regulated kinase signaling in melanoma cell lines. Cancer Res. 2004;64:5186-92 pubmed
    ..Taken together, our results suggest that loss of RKIP in malignant melanoma contributes to enhanced invasiveness of transformed cells and therefore to progression of the disease. ..
  13. Schoentgen F, Jolles P. From structure to function: possible biological roles of a new widespread protein family binding hydrophobic ligands and displaying a nucleotide binding site. FEBS Lett. 1995;369:22-6 pubmed
    ..These results imply that 21-23 kDa proteins function in oxidoreduction reactions and signal mechanisms during cell growth and maturation. ..
  14. Maresch J, Birner P, Zakharinov M, Toumangelova Uzeir K, Natchev S, Guentchev M. Additive effect on survival of Raf kinase inhibitor protein and signal transducer and activator of transcription 3 in high-grade glioma. Cancer. 2011;117:2499-504 pubmed publisher
  15. Eves E, Shapiro P, Naik K, Klein U, Trakul N, Rosner M. Raf kinase inhibitory protein regulates aurora B kinase and the spindle checkpoint. Mol Cell. 2006;23:561-74 pubmed
  16. Hahm J, Ahn J, Noh H, Baek S, Ha J, Jung T, et al. Comparative analysis of fat and muscle proteins in fenofibrate-fed type II diabetic OLETF rats: the fenofibrate-dependent expression of PEBP or C11orf59 protein. BMB Rep. 2010;43:337-43 pubmed
    ..Additionally, the signal proteins phosphatidylethanolamine binding protein and IkB interacting protein were differentially regulated in the fenofibrate-treated adipose ..
  17. Ruan L, Wang G, Yi H, Chen Y, Tang C, Zhang P, et al. Raf kinase inhibitor protein correlates with sensitivity of nasopharyngeal carcinoma to radiotherapy. J Cell Biochem. 2010;110:975-81 pubmed publisher
    ..The data suggested that RKIP was a potential biomarker for the radiosensitivity and prognosis of NPC, and its dysregulation might play an important role in the radioresistance of NPC. ..
  18. Granovsky A, Rosner M. Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor. Cell Res. 2008;18:452-7 pubmed publisher
    ..Raf Kinase Inhibitory Protein (RKIP), a member of the phosphatidylethanolamine binding protein (PEBP) family, is representative of a new class of modulators of signaling cascades that function ..
  19. Houben R, Vetter Kauczok C, Ortmann S, Rapp U, Broecker E, Becker J. Phospho-ERK staining is a poor indicator of the mutational status of BRAF and NRAS in human melanoma. J Invest Dermatol. 2008;128:2003-12 pubmed publisher
    ..Our findings suggest that mitogen-activated protein kinase (MAPK) activity is subject to regulation even in BRAF/NRAS mutant melanoma cells and that high MAPK pathway signaling may be important only in distinct subsets of tumor cells. ..
  20. Mc Henry K, Montesano R, Zhu S, Beshir A, Tang H, Yeung K, et al. Raf kinase inhibitor protein positively regulates cell-substratum adhesion while negatively regulating cell-cell adhesion. J Cell Biochem. 2008;103:972-85 pubmed
  21. Yamaguchi A, Kobayashi Y, Goto K, Abe M, Araki T. TWIN SISTER OF FT (TSF) acts as a floral pathway integrator redundantly with FT. Plant Cell Physiol. 2005;46:1175-89 pubmed
    ..We propose that the phloem is the site where multiple regulatory pathways are integrated at the transcriptional regulation of FT and TSF. ..
  22. Jazirehi A, Vega M, Chatterjee D, Goodglick L, Bonavida B. Inhibition of the Raf-MEK1/2-ERK1/2 signaling pathway, Bcl-xL down-regulation, and chemosensitization of non-Hodgkin's lymphoma B cells by Rituximab. Cancer Res. 2004;64:7117-26 pubmed
    ..The significance of these findings is discussed. ..
  23. Baritaki S, Bonavida B. Viral infection and cancer: the NF-kappaB/Snail/RKIP loop regulates target cell sensitivity to apoptosis by cytotoxic lymphocytes. Crit Rev Immunol. 2010;30:31-46 pubmed
    ..Alternative therapeutic interventions, such as various inhibitors, NF-kappaB inhibitors, and siRNAs, are presented. ..
  24. Shemon A, Heil G, Granovsky A, Clark M, McElheny D, Chimon A, et al. Characterization of the Raf kinase inhibitory protein (RKIP) binding pocket: NMR-based screening identifies small-molecule ligands. PLoS ONE. 2010;5:e10479 pubmed publisher
    ..The common structural elements of these compounds defines a minimal requirement for RKIP binding and thus they can be used as lead compounds for future design of RKIP ligands with therapeutic potential. ..
  25. Rath O, Park S, Tang H, Banfield M, Brady R, Lee Y, et al. The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated phosphorylation of MEK. Cell Signal. 2008;20:935-41 pubmed publisher
    ..Our results therefore suggest that the RKIP conserved pocket may constitute a novel phosphoamino-acid binding motif and is absolutely required for RKIP function. ..
  26. Wang X, Wang S, Tang X, Zhang A, Grabinski T, Guo Z, et al. Development and evaluation of monoclonal antibodies against phosphatidylethanolamine binding protein 1 in pancreatic cancer patients. J Immunol Methods. 2010;362:151-60 pubmed publisher
    b>Phosphatidylethanolamine binding protein 1 (PEBP1), also known as Raf kinase inhibitor protein (RKIP), has been considered as a suppressor of metastasis and a prognostic marker in prostate cancer, breast cancer, gastrointestinal stromal ..
  27. Clark M, McElheny D, Wojcik J, Kurutz J, Rosner M, Koide S. NMR assignment of rat Raf kinase inhibitor protein. J Biomol NMR. 2006;36 Suppl 1:4 pubmed
  28. Koelzer V, Karamitopoulou E, Dawson H, Kondi Pafiti A, Zlobec I, Lugli A. Geographic analysis of RKIP expression and its clinical relevance in colorectal cancer. Br J Cancer. 2013;108:2088-96 pubmed publisher
    ..0474). The clinical relevance of RKIP expression as an independent prognostic factor is restricted to the tumour centre. Loss of RKIP predicts features of EMT and correlates with frequent distant metastasis. ..
  29. Wang L, Li H, Zhang J, Lu W, Zhao J, Su L, et al. Phosphatidylethanolamine binding protein 1 in vacular endothelial cell autophagy and atherosclerosis. J Physiol. 2013;591:5005-15 pubmed publisher
    ..To further investigate the mechanism of PC-PLC action, we initially identified phosphatidylethanolamine binding protein 1 (PEBP1) as a binding partner of PC-PLC by using mass spectrometry (MS, MALDI-TOF/TOF)...
  30. Schuierer M, Heilmeier U, Boettcher A, Ugocsai P, Bosserhoff A, Schmitz G, et al. Induction of Raf kinase inhibitor protein contributes to macrophage differentiation. Biochem Biophys Res Commun. 2006;342:1083-7 pubmed
  31. Corbit K, Trakul N, Eves E, Diaz B, Marshall M, Rosner M. Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein. J Biol Chem. 2003;278:13061-8 pubmed
  32. Karlgren A, Gyllenstrand N, Källman T, Sundstrom J, Moore D, Lascoux M, et al. Evolution of the PEBP gene family in plants: functional diversification in seed plant evolution. Plant Physiol. 2011;156:1967-77 pubmed publisher
  33. Huerta Yepez S, Yoon N, Hernández Cueto A, Mah V, Rivera Pazos C, Chatterjee D, et al. Expression of phosphorylated raf kinase inhibitor protein (pRKIP) is a predictor of lung cancer survival. BMC Cancer. 2011;11:259 pubmed publisher
    ..This study examines for the first time, the expression profile of RKIP and phospho-RKIP in lung cancer. Significantly, we found that phospho-RKIP was a predictive indicator of survival. ..
  34. Kim H, Won K, Kim G, Kim S, Park Y, Kim Y. Reduced expression of Raf-1 kinase inhibitory protein predicts regional lymph node metastasis and shorter survival in esophageal squamous cell carcinoma. Pathol Res Pract. 2012;208:292-9 pubmed publisher
    ..004). Reduced RKIP expression in ESCC correlated with advanced disease, regional LNM and poor prognosis. RKIP expression may serve as a novel clinical biomarker in patients with ESCC. ..
  35. Keller E, Fu Z, Brennan M. The biology of a prostate cancer metastasis suppressor protein: Raf kinase inhibitor protein. J Cell Biochem. 2005;94:273-8 pubmed
    ..RKIP) was originally identified as a protein that bound membrane phospholipids and was named phosphatidylethanolamine binding protein-2 (PEBP-2)...
  36. Zaravinos A, Kanellou P, Baritaki S, Bonavida B, Spandidos D. BRAF and RKIP are significantly decreased in cutaneous squamous cell carcinoma. Cell Cycle. 2009;8:1402-8 pubmed
    ..Our results further indicate that BRAF does not appear to be frequently mutated either in pre-cancerous skin lesions (AK) or in non-melanoma skin tumors (SCC). ..
  37. Al Mulla F, Hagan S, Behbehani A, Bitar M, George S, Going J, et al. Raf kinase inhibitor protein expression in a survival analysis of colorectal cancer patients. J Clin Oncol. 2006;24:5672-9 pubmed
    ..5; 95% CI, 1.7 to 12.3; P = .003). RKIP expression in primary CRCs correlates with overall and disease-free survival, and can be useful for identifying early-stage CRC patients at risk of relapse. ..
  38. Gimenez M, Souza V, Izumi C, Barbieri M, Chammas R, Oba Shinjo S, et al. Proteomic analysis of low- to high-grade astrocytomas reveals an alteration of the expression level of raf kinase inhibitor protein and nucleophosmin. Proteomics. 2010;10:2812-21 pubmed publisher
    ..Due to the participation of NPM and RKIP in uncontrolled proliferation and evasion of apoptosis, these proteins are likely targets for drug development. ..
  39. Al Mulla F, Bitar M, Al Maghrebi M, Behbehani A, Al Ali W, Rath O, et al. Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3?. Cancer Res. 2011;71:1334-43 pubmed publisher
    ..RKIP levels in human colorectal cancer positively correlate with GSK3? expression. These findings reveal the RKIP/GSK3 axis as both a potential therapeutic target and a prognosis-based predictor of cancer progression. ..
  40. Maki M, Matsukawa N, Yuasa H, Otsuka Y, Yamamoto T, Akatsu H, et al. Decreased expression of hippocampal cholinergic neurostimulating peptide precursor protein mRNA in the hippocampus in Alzheimer disease. J Neuropathol Exp Neurol. 2002;61:176-85 pubmed
  41. George A, Holsinger R, McLean C, Tan S, Scott H, Cardamone T, et al. Decreased phosphatidylethanolamine binding protein expression correlates with Abeta accumulation in the Tg2576 mouse model of Alzheimer's disease. Neurobiol Aging. 2006;27:614-23 pubmed
    b>Phosphatidylethanolamine binding protein (PEBP) is a multifunctional protein, with proposed roles as the precursor protein of hippocampal cholinergic neurostimulating peptide (HCNP), and as the Raf kinase inhibitor protein (RKIP)...
  42. Theroux S, Pereira M, Casten K, Burwell R, Yeung K, Sedivy J, et al. Raf kinase inhibitory protein knockout mice: expression in the brain and olfaction deficit. Brain Res Bull. 2007;71:559-67 pubmed
    ..In the brain, expression was ubiquitous in limbic formations, and homozygous mice developed olfaction deficits in the first year of life. We postulate that RKIP-1 may be a modulator of behavioral responses. ..
  43. Chatterjee D, Sabo E, Tavares R, Resnick M. Inverse association between Raf Kinase Inhibitory Protein and signal transducers and activators of transcription 3 expression in gastric adenocarcinoma patients: implications for clinical outcome. Clin Cancer Res. 2008;14:2994-3001 pubmed publisher
    ..Significantly, we show an inverse association between RKIP and STAT3 and a positive correlation between RKIP and patient survival. ..
  44. Hagan S, Al Mulla F, Mallon E, Oien K, Ferrier R, Gusterson B, et al. Reduction of Raf-1 kinase inhibitor protein expression correlates with breast cancer metastasis. Clin Cancer Res. 2005;11:7392-7 pubmed
    ..RKIP expression is independent of other markers for breast cancer progression and prognosis. ..
  45. Huang L, Chen S, Luo W, Jiang H, Zhang P, Yi H. Proteomic analysis of secreted proteins of non-small cell lung cancer. Ai Zheng. 2006;25:1361-7 pubmed
    ..which included peptidyl-prolyl cis-trans isomerase A (PPIA), Mn-SOD, peroxiredoxin 1 (PDX1), phosphatidylethanolamine binding protein (PEBP), glutathione S-transferase P (GSTP1-1), glucose-dependent insulinotropic protein receptor (..
  46. Mathieu J, Warthmann N, Küttner F, Schmid M. Export of FT protein from phloem companion cells is sufficient for floral induction in Arabidopsis. Curr Biol. 2007;17:1055-60 pubmed
    ..Furthermore, we have devised a method that uncouples FT mRNA and protein effects in vivo. We demonstrate that export of FT protein from phloem companion cells is sufficient to induce flowering. ..
  47. Kim W, Ahn H, Chiou T, Ahn J. The role of the miR399-PHO2 module in the regulation of flowering time in response to different ambient temperatures in Arabidopsis thaliana. Mol Cells. 2011;32:83-8 pubmed publisher
    ..Taken together, our results suggest that miR399, an ambient temperature-responsive miRNA, plays a role in ambient temperature-responsive flowering in Arabidopsis. ..
  48. Chatterjee D, Bai Y, Wang Z, Beach S, Mott S, Roy R, et al. RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. J Biol Chem. 2004;279:17515-23 pubmed
  49. Bonavida B, Baritaki S, Huerta Yepez S, Vega M, Chatterjee D, Yeung K. Novel therapeutic applications of nitric oxide donors in cancer: roles in chemo- and immunosensitization to apoptosis and inhibition of metastases. Nitric Oxide. 2008;19:152-7 pubmed publisher
    ..Thus, nitric oxide donors have the dual functions of both sensitizing tumor cells to chemotherapy and immunotherapy and are also involved in the regulation and inhibition of metastasis. ..
  50. Wang X, Li N, Li H, Liu B, Qiu J, Chen T, et al. Silencing of human phosphatidylethanolamine-binding protein 4 sensitizes breast cancer cells to tumor necrosis factor-alpha-induced apoptosis and cell growth arrest. Clin Cancer Res. 2005;11:7545-53 pubmed
    ..Silencing of hPEBP4 expression may be a promising approach for the treatment of breast carcinoma. ..
  51. Qiu J, Xiao J, Han C, Li N, Shen X, Jiang H, et al. Potentiation of tumor necrosis factor-alpha-induced tumor cell apoptosis by a small molecule inhibitor for anti-apoptotic protein hPEBP4. J Biol Chem. 2010;285:12241-7 pubmed publisher
    ..Taken together, our data suggest that IOI-42, as the first chemical inhibitor of anti-apoptotic protein hPEBP4, may serve as a potential anti-tumor drug by sensitizing tumor cells to apoptotic inducers. ..
  52. Doyle B, Hagan S, Al Mulla F, Scott L, Harden S, Paul J, et al. Raf kinase inhibitor protein expression combined with peritoneal involvement and lymphovascular invasion predicts prognosis in Dukes' B colorectal cancer patients. Histopathology. 2013;62:505-10 pubmed
    ..It is this high-risk group which is most likely to benefit from close postoperative monitoring and may derive the most benefit from adjuvant therapy. ..
  53. Zlobec I, Baker K, Minoo P, Jass J, Terracciano L, Lugli A. Node-negative colorectal cancer at high risk of distant metastasis identified by combined analysis of lymph node status, vascular invasion, and Raf-1 kinase inhibitor protein expression. Clin Cancer Res. 2008;14:143-8 pubmed publisher
    ..Additionally, a subgroup of more aggressive N(0) tumors can be identified by evaluating vascular invasion and RKIP expression. ..
  54. Zhang L, Fu Z, Binkley C, Giordano T, Burant C, Logsdon C, et al. Raf kinase inhibitory protein inhibits beta-cell proliferation. Surgery. 2004;136:708-15 pubmed
    ..We also showed that RKIP inhibited beta-cell proliferation by altering cell cycle distribution, rather than by promoting apoptosis. RKIP is important in beta-cell proliferation, and its downregulation may play a role in islet neoplasia. ..
  55. Moffit J, Boekelheide K, Sedivy J, Klysik J. Mice lacking Raf kinase inhibitor protein-1 (RKIP-1) have altered sperm capacitation and reduced reproduction rates with a normal response to testicular injury. J Androl. 2007;28:883-90 pubmed
    ..Overall, these studies indicate an important role for RKIP in reproduction as a modulator of capacitation but not in the regulation of testicular injury. ..
  56. Xu Y, Yi Y, Qiu S, Gao Q, Li Y, Dai C, et al. PEBP1 downregulation is associated to poor prognosis in HCC related to hepatitis B infection. J Hepatol. 2010;53:872-9 pubmed publisher
    ..Down-regulation of PEBP1 in HCC indicated aggressive tumor behaviors and predicted a worse clinical outcome, which may be a useful biomarker to identify the patients at high risk of post-operative recurrence. ..
  57. Hu C, Zhou L, Zhang J, Huang C, Zhang G. Immunohistochemical detection of Raf kinase inhibitor protein in normal cervical tissue and cervical cancer tissue. J Int Med Res. 2011;39:229-37 pubmed
    ..RKIP positivity correlated inversely with LNM. RKIP may play a role in cervical-cancer genesis and metastasis; RKIP down-regulation was associated with metastatic disease in human cervical cancer. ..
  58. Chardon F, Damerval C. Phylogenomic analysis of the PEBP gene family in cereals. J Mol Evol. 2005;61:579-90 pubmed
    ..A phylogenomic approach leads to some hypotheses about conservation of gene function within the subfamilies. ..
  59. Baritaki S, Chapman A, Yeung K, Spandidos D, Palladino M, Bonavida B. Inhibition of epithelial to mesenchymal transition in metastatic prostate cancer cells by the novel proteasome inhibitor, NPI-0052: pivotal roles of Snail repression and RKIP induction. Oncogene. 2009;28:3573-85 pubmed publisher
    ..These findings demonstrate, for the first time, the role of NPI-0052 in the regulation of EMT via inhibition of NF-kappaB and Snail and induction of RKIP. ..
  60. Li H, Gao Y, Zhao X, Liu Y, Sun B, Yang J, et al. Effects of raf kinase inhibitor protein expression on metastasis and progression of human breast cancer. Mol Cancer Res. 2009;7:832-40 pubmed publisher
    ..These results indicate that RKIP is a metastasis suppressor gene of human breast cancer. ..
  61. Liu H, Kong Q, Li B, He Y, Li P, Jia B. Expression of PEBP4 protein correlates with the invasion and metastasis of colorectal cancer. Tumour Biol. 2012;33:267-73 pubmed publisher
    ..05). The over-expression of PEBP4 protein may be related to the tumorigenesis, development, metastasis, and invasion of colorectal cancer. ..
  62. Dangi Garimella S, Yun J, Eves E, Newman M, Erkeland S, Hammond S, et al. Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. EMBO J. 2009;28:347-58 pubmed publisher
    ..RKIP regulation of two pluripotent stem cell genes, Myc and LIN28, highlights the importance of RKIP as a key metastasis suppressor and potential therapeutic agent. ..
  63. Yu G, Chen G, Wu S, Shen K, Ji Y. The expression of PEBP4 protein in lung squamous cell carcinoma. Tumour Biol. 2011;32:1257-63 pubmed publisher
    ..05); however, this was unrelated to the gender, age, or tumor size of the patient (p?>?0.05). PEBP4 protein overexpression was associated with the occurrence, invasion, and metastasis of lung squamous cell carcinoma. ..
  64. Lorenz K, Lohse M, Quitterer U. Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature. 2003;426:574-9 pubmed
    ..A physiological role for this mechanism is shown in cardiomyocytes in which the downregulation of RKIP restrains beta-adrenergic signalling and contractile activity. ..
  65. Wang X, Li N, Liu B, Sun H, Chen T, Li H, et al. A novel human phosphatidylethanolamine-binding protein resists tumor necrosis factor alpha-induced apoptosis by inhibiting mitogen-activated protein kinase pathway activation and phosphatidylethanolamine externalization. J Biol Chem. 2004;279:45855-64 pubmed
  66. Odabaei G, Chatterjee D, Jazirehi A, Goodglick L, Yeung K, Bonavida B. Raf-1 kinase inhibitor protein: structure, function, regulation of cell signaling, and pivotal role in apoptosis. Adv Cancer Res. 2004;91:169-200 pubmed
    ..Also, induction of RKIP by drugs or anti-receptor antibodies sensitizes cancer cells to drug-induced apoptosis. In this review, we discuss the discovery, structure, function, and significance of RKIP in cancer. ..
  67. Feldmann R, Maurer M, Hunzinger C, Lewicka S, Buergers H, Kalenka A, et al. Reduction in rat phosphatidylethanolamine binding protein-1 (PEBP1) after chronic corticosterone treatment may be paralleled by cognitive impairment: a first study. Stress. 2008;11:134-47 pubmed publisher
    ..mimic of experimentally induced stress affects psychometric performance and the expression of the phosphatidylethanolamine binding protein (PEBP1) in the adult hippocampus of one-year-old male rats...
  68. Wu K, Bonavida B. The activated NF-kappaB-Snail-RKIP circuitry in cancer regulates both the metastatic cascade and resistance to apoptosis by cytotoxic drugs. Crit Rev Immunol. 2009;29:241-54 pubmed
    ..Thus, pharmacological agents regulating the RKIP-NF-kappaB-Snail loop can be used as both sensitizing agents for apoptosis when combined with cytotoxic therapies as well as inhibitors of metastasis. ..
  69. Chen Y, Tang C, Ouyang G, Ruan L, Li M, Zhang P, et al. Identification of RKIP as a differentially tyrosine-phosphorylated protein in nasopharyngeal carcinoma and normal nasopharyngeal epithelial tissues by phosphoproteomic approach. Med Oncol. 2009;26:463-70 pubmed publisher
    ..The 13 differentially tyrosine-phosphorylated proteins may be involved in the development and progression of NPC. ..
  70. Akaishi J, Onda M, Asaka S, Okamoto J, Miyamoto S, Nagahama M, et al. Growth-suppressive function of phosphatidylethanolamine-binding protein in anaplastic thyroid cancer. Anticancer Res. 2006;26:4437-42 pubmed
    ..This is the first report demonstrating that PBP may be a tumor suppressor whose loss is associated with development of anaplastic thyroid cancer from differentiated thyroid cancer. ..
  71. Huang J, Mahavadi S, Sriwai W, Grider J, Murthy K. Cross-regulation of VPAC(2) receptor desensitization by M(3) receptors via PKC-mediated phosphorylation of RKIP and inhibition of GRK2. Am J Physiol Gastrointest Liver Physiol. 2007;292:G867-74 pubmed
    ..The mechanism involved phosphorylation of RKIP by PKC, switching RKIP from association with Raf-1 to association with, and inhibition of, GRK2. ..
  72. Hengst U, Albrecht H, Hess D, Monard D. The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors. J Biol Chem. 2001;276:535-40 pubmed
    ..PEBP immunoreactivity is found on the surface of Rat-1 fibroblast cells and although its sequence contains no secretion signal, PEBP-H(6) can be purified from the conditioned medium upon recombinant expression. ..
  73. Banfield M, Barker J, Perry A, Brady R. Function from structure? The crystal structure of human phosphatidylethanolamine-binding protein suggests a role in membrane signal transduction. Structure. 1998;6:1245-54 pubmed
    ..These studies are consistent with a primary biological role for hPEBP as a transducer of signals from the interior membrane surface. ..
  74. Tavel L, Jaquillard L, Karsisiotis A, Saab F, Jouvensal L, Brans A, et al. Ligand binding study of human PEBP1/RKIP: interaction with nucleotides and Raf-1 peptides evidenced by NMR and mass spectrometry. PLoS ONE. 2012;7:e36187 pubmed publisher
    Human Phosphatidylethanolamine binding protein 1 (hPEBP1) also known as Raf kinase inhibitory protein (RKIP), affects various cellular processes, and is implicated in metastasis formation and Alzheimer's disease...
  75. Al Mulla F, Bitar M, Feng J, Park S, Yeung K. A new model for raf kinase inhibitory protein induced chemotherapeutic resistance. PLoS ONE. 2012;7:e29532 pubmed publisher
    ..Our data illuminate, for the first time, the NRF2-KEAP 1 pathway as a possible target for personalized therapeutic intervention in RKIP depleted cancers. ..
  76. Karamitopoulou E, Zlobec I, Panayiotides I, Patsouris E, Peros G, Rallis G, et al. Systematic analysis of proteins from different signaling pathways in the tumor center and the invasive front of colorectal cancer. Hum Pathol. 2011;42:1888-96 pubmed publisher
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  78. Martinho O, Gouveia A, Silva P, Pimenta A, Reis R, Lopes J. Loss of RKIP expression is associated with poor survival in GISTs. Virchows Arch. 2009;455:277-84 pubmed publisher
    ..So far, this is the first study assessing RKIP expression levels in GISTs. We conclude that loss of RKIP expression could have an important role as prognostic marker in GISTs. ..
  79. Woods Ignatoski K, Grewal N, Markwart S, Vellaichamy A, Chinnaiyan A, Yeung K, et al. Loss of Raf kinase inhibitory protein induces radioresistance in prostate cancer. Int J Radiat Oncol Biol Phys. 2008;72:153-60 pubmed publisher
    ..Therefore, it is conceivable that the loss of RKIP confers a growth advantage on PCa cells at distant sites, because the loss of RKIP would decrease apoptosis, favoring proliferation. ..