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Gene Review

IFI27  -  interferon, alpha-inducible protein 27

Homo sapiens

Synonyms: FAM14D, ISG12, ISG12(a), ISG12A, Interferon alpha-induced 11.5 kDa protein, ...
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Disease relevance of IFI27


Psychiatry related information on IFI27


High impact information on IFI27

  • In this issue, two papers () address this problem by reporting phosphorylation of the cyclin-dependent kinase inhibitor p27(Kip1) on a tyrosine residue by nonreceptor tyrosine kinases, which decreases p27 stability [7].
  • Y88 phosphorylation does not prevent p27 binding to cyclin A/Cdk2 [8].
  • This direct link between transforming tyrosine kinases and p27 may provide an explanation for Cdk kinase activities observed in p27 complexes and for premature p27 elimination in cells that have been transformed by activated tyrosine kinases [8].
  • A conserved tyrosine residue (Y88) in the Cdk-binding domain of p27 can be phosphorylated by the Src-family kinase Lyn and the oncogene product BCR-ABL [8].
  • Instead, it causes phosphorylated Y88 and the entire inhibitory 3(10)-helix of p27 to be ejected from the Cdk2 active site, thus restoring partial Cdk activity [8].

Chemical compound and disease context of IFI27


Biological context of IFI27

  • In addition, these results suggest that there is a link between p27 expression and the ability of CLL cells to undergo apoptosis [14].
  • The relation of TGF-beta 1 stimulation to p21 and p27 was examined using a fine-mapping approach to gene expression in individual cells [15].
  • Although multiple factors influence pRb phosphorylation, it appears that both cyclin D1 and p21 expression do not change in the presence of DHA, although p27 was strikingly increased in SK-Mel-110 cells in the absence of FBS [16].
  • The involvement of p27 in the negative regulation of cell proliferation suggests that it may also function as a tumor suppressor gene [17].
  • Identification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in breast carcinoma [4].

Anatomical context of IFI27

  • IFI27 mRNA expression was highly upregulated in lesional psoriatic epidermis and also detected in non-lesional keratinocytes [1].
  • In contrast to the widespread expression of p21 and p27 in human tissues, p57 is expressed in a tissue-specific manner, as a 1.5-kb species in placenta and at lower levels in various other tissues and a 7-kb mRNA species observed in skeletal muscle and heart [18].
  • In B-CLL, p27 levels were independent of absolute number of circulating lymphocytes, but strongly correlated with both lymphocyte and total tumor mass (TTM) doubling time [14].
  • Investigations in a human mammary epithelial cell (HMEC) model, including cells that are sensitive (184(S)) and resistant (184A1L5(R)) to G(1) arrest by TGF-beta, revealed aberrant p27 regulation in the resistant cells [19].
  • Skp2 is required for endothelial cell proliferation as a consequence of degrading p27 [20].

Associations of IFI27 with chemical compounds


Physical interactions of IFI27

  • Despite a reduction in total and cyclin E-Cdk2 bound p27 after ASp27 transfection, HMECs remained arrested in the G(1) phase [24].
  • Here we show that Bcr-Abl tyrosine kinase facilitates the down-regulation of p27 by modulating complex formation of Jab1/CSN through the mitogen-activated protein (MAP) kinase and phosphatidylinositol 3 (PI3) kinase signaling pathways [25].
  • Finally, binding of Max was shown to facilitate c-Myc binding and repression of p27 promoter activity [26].
  • The degradation of Skp2 stabilizes p27, thereby ensuring TGF-beta-induced cell cycle arrest [27].
  • We report here that Skp2 is rapidly degraded following cellular stimulation by the cytokine transforming growth factor beta (TGF-beta) and that this degradation stabilizes the cell cycle arrest protein p27 [27].

Enzymatic interactions of IFI27

  • Transduction of BT-474 cells with an adenovirus-encoding active (myristoylated) Akt (Myr-Akt), but not with a beta-galactosidase control adenovirus, prevented the Herceptin- or LY294002-induced down-regulation of cyclin D1 and of phosphorylated GSK-3beta and prevented the accumulation of p27 in the nucleus and cytosol [28].

Regulatory relationships of IFI27


Other interactions of IFI27


Analytical, diagnostic and therapeutic context of IFI27

  • The expression of cell cycle-regulating proteins, such as p21, p27, p18(INK4c), cyclin E, and pRb, was examined using Western blotting [10].
  • In univariate analysis, cases with p27 LI < 50 (P =.0004), cyclin D1 overexpression (P =.0041), and cyclin E overexpression (P =.0572, borderline significance) showed poorer outcomes for disease-free survival (DFS) [38].
  • We assessed p27 and p53 expressions by immunohistochemistry [39].
  • Among these, an interferon-induced gene, IFI27, was differentially expressed among all three types of HCCs, and this result was confirmed by RT-PCR [40].
  • Two homozygous deletions of the p27 gene were detected in one case of B-immunoblastic NHL and in one case of acute ATL by Southern blot hybridization [41].


  1. Interferon alpha-inducible protein 27 (IFI27) is upregulated in psoriatic skin and certain epithelial cancers. Suomela, S., Cao, L., Bowcock, A., Saarialho-Kere, U. J. Invest. Dermatol. (2004) [Pubmed]
  2. Isolation and expression profiling of genes upregulated in the peripheral blood cells of systemic lupus erythematosus patients. Ishii, T., Onda, H., Tanigawa, A., Ohshima, S., Fujiwara, H., Mima, T., Katada, Y., Deguchi, H., Suemura, M., Miyake, T., Miyatake, K., Kawase, I., Zhao, H., Tomiyama, Y., Saeki, Y., Nojima, H. DNA Res. (2005) [Pubmed]
  3. Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells. Cariou, S., Donovan, J.C., Flanagan, W.M., Milic, A., Bhattacharya, N., Slingerland, J.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. Identification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in breast carcinoma. Rasmussen, U.B., Wolf, C., Mattei, M.G., Chenard, M.P., Bellocq, J.P., Chambon, P., Rio, M.C., Basset, P. Cancer Res. (1993) [Pubmed]
  5. Increased p27, an essential component of cell cycle control, in Alzheimer's disease. Ogawa, O., Lee, H.G., Zhu, X., Raina, A., Harris, P.L., Castellani, R.J., Perry, G., Smith, M.A. Aging Cell (2003) [Pubmed]
  6. Erythropoietin protects dopaminergic neurons and improves neurobehavioral outcomes in juvenile rats after neonatal hypoxia-ischemia. Demers, E.J., McPherson, R.J., Juul, S.E. Pediatr. Res. (2005) [Pubmed]
  7. Another Piece of the p27(Kip1) Puzzle. Kaldis, P. Cell (2007) [Pubmed]
  8. Cdk-Inhibitory Activity and Stability of p27(Kip1) Are Directly Regulated by Oncogenic Tyrosine Kinases. Grimmler, M., Wang, Y., Mund, T., Cilensek, Z., Keidel, E.M., Waddell, M.B., Jäkel, H., Kullmann, M., Kriwacki, R.W., Hengst, L. Cell (2007) [Pubmed]
  9. The dual ErbB1/ErbB2 inhibitor, lapatinib (GW572016), cooperates with tamoxifen to inhibit both cell proliferation- and estrogen-dependent gene expression in antiestrogen-resistant breast cancer. Chu, I., Blackwell, K., Chen, S., Slingerland, J. Cancer Res. (2005) [Pubmed]
  10. Involvement of p21(WAF1/Cip1), p27(Kip1), and p18(INK4c) in troglitazone-induced cell-cycle arrest in human hepatoma cell lines. Koga, H., Sakisaka, S., Harada, M., Takagi, T., Hanada, S., Taniguchi, E., Kawaguchi, T., Sasatomi, K., Kimura, R., Hashimoto, O., Ueno, T., Yano, H., Kojiro, M., Sata, M. Hepatology (2001) [Pubmed]
  11. Protein levels of p21, p27, cyclin E and Bax predict sensitivity to cisplatin and paclitaxel in head and neck squamous cell carcinomas. Taguchi, T., Kato, Y., Baba, Y., Nishimura, G., Tanigaki, Y., Horiuchi, C., Mochimatsu, I., Tsukuda, M. Oncol. Rep. (2004) [Pubmed]
  12. 1,25(OH)2 vitamin D3 induces elevated expression of the cell cycle-regulating genes P21 and P27 in squamous carcinoma cell lines of the head and neck. Hager, G., Formanek, M., Gedlicka, C., Thurnher, D., Knerer, B., Kornfehl, J. Acta Otolaryngol. (2001) [Pubmed]
  13. Vitamin D and its analog EB1089 induce p27 accumulation and diminish association of p27 with Skp2 independent of PTEN in pituitary corticotroph cells. Liu, W., Asa, S.L., Ezzat, S. Brain Pathol. (2002) [Pubmed]
  14. Prognostic significance of the cell cycle inhibitor p27Kip1 in chronic B-cell lymphocytic leukemia. Vrhovac, R., Delmer, A., Tang, R., Marie, J.P., Zittoun, R., Ajchenbaum-Cymbalista, F. Blood (1998) [Pubmed]
  15. Transforming growth factor beta 1 mediates cell-cycle arrest of primitive hematopoietic cells independent of p21(Cip1/Waf1) or p27(Kip1). Cheng, T., Shen, H., Rodrigues, N., Stier, S., Scadden, D.T. Blood (2001) [Pubmed]
  16. Cell cycle arrest and apoptosis of melanoma cells by docosahexaenoic acid: association with decreased pRb phosphorylation. Albino, A.P., Juan, G., Traganos, F., Reinhart, L., Connolly, J., Rose, D.P., Darzynkiewicz, Z. Cancer Res. (2000) [Pubmed]
  17. p27Kip1: chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumors. Ponce-Castañeda, M.V., Lee, M.H., Latres, E., Polyak, K., Lacombe, L., Montgomery, K., Mathew, S., Krauter, K., Sheinfeld, J., Massague, J. Cancer Res. (1995) [Pubmed]
  18. Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Lee, M.H., Reynisdóttir, I., Massagué, J. Genes Dev. (1995) [Pubmed]
  19. Altered p27(Kip1) phosphorylation, localization, and function in human epithelial cells resistant to transforming growth factor beta-mediated G(1) arrest. Ciarallo, S., Subramaniam, V., Hung, W., Lee, J.H., Kotchetkov, R., Sandhu, C., Milic, A., Slingerland, J.M. Mol. Cell. Biol. (2002) [Pubmed]
  20. Focal adhesion kinase controls cellular levels of p27/Kip1 and p21/Cip1 through Skp2-dependent and -independent mechanisms. Bryant, P., Zheng, Q., Pumiglia, K. Mol. Cell. Biol. (2006) [Pubmed]
  21. Apigenin inhibits endothelial-cell proliferation in G(2)/M phase whereas it stimulates smooth-muscle cells by inhibiting P21 and P27 expression. Trochon, V., Blot, E., Cymbalista, F., Engelmann, C., Tang, R.P., Thomaïdis, A., Vasse, M., Soria, J., Lu, H., Soria, C. Int. J. Cancer (2000) [Pubmed]
  22. Artepillin C in Brazilian propolis induces G(0)/G(1) arrest via stimulation of Cip1/p21 expression in human colon cancer cells. Shimizu, K., Das, S.K., Hashimoto, T., Sowa, Y., Yoshida, T., Sakai, T., Matsuura, Y., Kanazawa, K. Mol. Carcinog. (2005) [Pubmed]
  23. Monensin-mediated growth inhibition of SNU-C1 colon cancer cells via cell cycle arrest and apoptosis. Park, W.H., Kim, E.S., Jung, C.W., Kim, B.K., Lee, Y.Y. Int. J. Oncol. (2003) [Pubmed]
  24. Non-malignant and tumor-derived cells differ in their requirement for p27Kip1 in transforming growth factor-beta-mediated G1 arrest. Donovan, J.C., Rothenstein, J.M., Slingerland, J.M. J. Biol. Chem. (2002) [Pubmed]
  25. The Jab1/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression. Tomoda, K., Kato, J.Y., Tatsumi, E., Takahashi, T., Matsuo, Y., Yoneda-Kato, N. Blood (2005) [Pubmed]
  26. Repression of transcription of the p27(Kip1) cyclin-dependent kinase inhibitor gene by c-Myc. Yang, W., Shen, J., Wu, M., Arsura, M., FitzGerald, M., Suldan, Z., Kim, D.W., Hofmann, C.S., Pianetti, S., Romieu-Mourez, R., Freedman, L.P., Sonenshein, G.E. Oncogene (2001) [Pubmed]
  27. Cdh1-Anaphase-Promoting Complex Targets Skp2 for Destruction in Transforming Growth Factor {beta}-Induced Growth Inhibition. Liu, W., Wu, G., Li, W., Lobur, D., Wan, Y. Mol. Cell. Biol. (2007) [Pubmed]
  28. Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Yakes, F.M., Chinratanalab, W., Ritter, C.A., King, W., Seelig, S., Arteaga, C.L. Cancer Res. (2002) [Pubmed]
  29. Effects of transforming growth factor beta 1 on the growth of rhabdomyosarcoma cell line RD. Ye, L., Zhang, H.Y., Wang, H., Yang, G.H., Bu, H., Zhang, L., Wang, S.L. Chin. Med. J. (2005) [Pubmed]
  30. Domain 5 of kininogen inhibits proliferation of human colon cancer cell line (HCT-116) by interfering with G1/S in the cell cycle. Bior, A.D., Pixley, R.A., Colman, R.W. J. Thromb. Haemost. (2007) [Pubmed]
  31. Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 with cyclin A-Cdk2 and cyclin D2-Cdk4. Blain, S.W., Montalvo, E., Massagué, J. J. Biol. Chem. (1997) [Pubmed]
  32. Over-expression of p27kip1 induces growth arrest and apoptosis mediated by changes of pRb expression in lung cancer cell lines. Naruse, I., Hoshino, H., Dobashi, K., Minato, K., Saito, R., Mori, M. Int. J. Cancer (2000) [Pubmed]
  33. Effects of thrombopoietin, interleukin-3 and the kinase inhibitor K-252a on growth and polyploidization of the megakaryocytic cell line M-07e. Quentmeier, H., Zaborski, M., Drexler, H.G. Leukemia (1998) [Pubmed]
  34. Expression of p21(Cip1/Waf1/Sdi1) and p27(Kip1) cyclin-dependent kinase inhibitors during human hematopoiesis. Taniguchi, T., Endo, H., Chikatsu, N., Uchimaru, K., Asano, S., Fujita, T., Nakahata, T., Motokura, T. Blood (1999) [Pubmed]
  35. CDK2 is a target for retinoic acid-mediated growth inhibition in MCF-7 human breast cancer cells. Teixeira, C., Pratt, M.A. Mol. Endocrinol. (1997) [Pubmed]
  36. Proteasome-dependent degradation of p27/kip1 in gliomas. Piva, R., Cancelli, I., Cavalla, P., Bortolotto, S., Dominguez, J., Draetta, G.F., Schiffer, D. J. Neuropathol. Exp. Neurol. (1999) [Pubmed]
  37. Proteinase 3 sidesteps caspases and cleaves p21(Waf1/Cip1/Sdi1) to induce endothelial cell apoptosis. Pendergraft, W.F., Rudolph, E.H., Falk, R.J., Jahn, J.E., Grimmler, M., Hengst, L., Jennette, J.C., Preston, G.A. Kidney Int. (2004) [Pubmed]
  38. Expression and prognostic roles of the G1-S modulators in hepatocellular carcinoma: p27 independently predicts the recurrence. Ito, Y., Matsuura, N., Sakon, M., Miyoshi, E., Noda, K., Takeda, T., Umeshita, K., Nagano, H., Nakamori, S., Dono, K., Tsujimoto, M., Nakahara, M., Nakao, K., Taniguchi, N., Monden, M. Hepatology (1999) [Pubmed]
  39. Loss of nuclear p27 (CDKN1B/KIP1) in colorectal cancer is correlated with microsatellite instability and CIMP. Ogino, S., Kawasaki, T., Kirkner, G.J., Yamaji, T., Loda, M., Fuchs, C.S. Mod. Pathol. (2007) [Pubmed]
  40. Molecular signature in three types of hepatocellular carcinoma with different viral origin by oligonucleotide microarray. Iizuka, N., Oka, M., Yamada-Okabe, H., Hamada, K., Nakayama, H., Mori, N., Tamesa, T., Okada, T., Takemoto, N., Matoba, K., Takashima, M., Sakamoto, K., Tangoku, A., Miyamoto, T., Uchimura, S., Hamamoto, Y. Int. J. Oncol. (2004) [Pubmed]
  41. Alterations of the p27KIP1 gene in non-Hodgkin's lymphomas and adult T-cell leukemia/lymphoma. Morosétti, R., Kawamata, N., Gombart, A.F., Miller, C.W., Hatta, Y., Hirama, T., Said, J.W., Tomonaga, M., Koeffler, H.P. Blood (1995) [Pubmed]
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