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Gene Review

CRLF1  -  cytokine receptor-like factor 1

Homo sapiens

Synonyms: CISS, CISS1, CLF, CLF-1, Cytokine receptor-like factor 1, ...
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Disease relevance of CRLF1

  • Signaling pathways recruited by the CLC/CLF complex in human neuroblastoma cell lines were also analyzed in detail [1].
  • In this study, we isolated a HL-60 variant cell line, HL-NR6, that is resistant to DETA/NO toxicity as assessed by DNA fragmentation, morphology, and colony forming ability [2].
  • With the exception of Staphylococcus aureus, which was recovered more often from VITAL aerobic bottles, more pathogenic microorganisms were recovered from BACTEC NR6 (aerobic) bottles than from VITAL aerobic bottles [3].
  • The CM of a minority (15/50) of cancers and one benign tissue had highly transforming activity for NR6 cells, and was mitogenic for a breast cancer cell line, was heat labile, and strongly heparin binding, eluting at 1.5-2.0 M salt [4].
  • OBJECTIVE: To assess the value of constructive interference in steady-state, three-dimensional, Fourier transformation (CISS) magnetic resonance imaging in the endoscopic management of hydrocephalus and intracranial cysts [5].

Psychiatry related information on CRLF1


High impact information on CRLF1

  • Analysis of transgenes carrying AG regulatory sequences confirms that H3K27me3 can spread to novel sequences in a CLF-dependent manner and further shows that H3K27me3 methylation is not sufficient for silencing of targets [7].
  • However, CLF is not itself an epigenetic mark as it is lost during mitosis [7].
  • Using chromatin immunoprecipitation, we identify AG and STM as direct targets for CLF and show that they carry a characteristic epigenetic signature of dispersed histone H3 lysine 27 trimethylation (H3K27me3) and localised H3K27me2 methylation [7].
  • In the present study, we show that differentiation and growth of hemopoietic stem cells in vitro from an invertebrate, Pacifastacus leniusculus, require an endogenous cytokine-like factor, astakine, containing a prokineticin (PK) domain [8].
  • Importantly, we found that CLC interacts with the soluble forms of CNTFRalpha and CLF via sites 1 and 3, respectively [9].

Chemical compound and disease context of CRLF1

  • A T2* weighted 3D CISS sequence (TR 14.65 ms, TE 21 ms, flip angle 65 degrees, voxel size 0.7 x 0.7 x 0.7 mm3) and a T1 weighted 3D MP-RAGE sequence (TR 12.5 ms, TE 5 ms, T1 300 ms, flip angle 15 degrees, voxel size 1.0 x 0.9 x 0.9 mm3) with and without contrast medium (gadolinium-DTPA, 0.1 mmol kg-1 body weight) were used [10].
  • Assessment of bacteraemia has been made at weekly intervals in 36 lepromatous leprosy patients who were put on different antileprosy drug under four regimens, viz., DDS alone, DDS in combination with rifampicin (DDS + RIF), clofazimine (DDS + CLF) and thiacetazone (DDS + TCT) [11].

Biological context of CRLF1

  • The Norwegian, Israeli and Canadian cases were homozygous or compound heterozygous, respectively, for mutations in the CRLF1 gene on chromosome 19p12 (CISS1) [12].
  • These results suggest that CLF-1 is a novel soluble cytokine receptor subunit or part of a novel cytokine complex, possibly playing a regulatory role in the immune system and during fetal development [13].
  • H3K27 methylation is present throughout leaf development and consistent with this, CLF is required persistently to silence AG [7].
  • Engineered NR6 cells that overexpress the HER-2 gene product display a highly transformed and tumorigenic phenotype as compared with control cells [14].
  • In this study, we isolated three petunia CLF-like genes (PhCLF1, PhCLF2 and PhCLF3) based on the sequence homology between CLF and E(Z) [15].

Anatomical context of CRLF1

  • The highest levels of hCLF-1 mRNA were observed in lymph node, spleen, thymus, appendix, placenta, stomach, bone marrow, and fetal lung, with constitutive expression of CLF-1 mRNA detected in a human kidney fibroblastic cell line [13].
  • Treatment of human neutrophils (PMN) with a cytokine-like factor in the supernatants of human lymphoblastoid cells (Raji) increased the random mobility and enhanced the migration of treated cells in response to other chemoattractants nearly 21/2-fold, although the supernatant itself was not a chemoattractant [16].
  • Analysis of peripheral blood lymphocytes from the parents by G banding and CISS showed a more complex translocation in the father: 46,XY,-2,-11,-22, +der(2) t(2;11)(q13;q23), +der(11) t(11;22) (q23;q11.2), +der(22) t(2;22) (q13;q11.2) [17].
  • We also observed that ROS generation following DETA/NO exposure was substantially higher in HL-60 cells than in HL-NR6 cells, using the 2',7'-dichlorofluorescein fluorometric method [2].
  • PURPOSE: To assess the value of a three-dimensional Fourier transformation MR technique "CISS" (constructive interference in steady state) in imaging the inner ear [18].

Associations of CRLF1 with chemical compounds

  • We found suggestive evidence of association (nominal P<0.01) with four genes (C3, FCER2, IL12RB1, and CRLF1) in a screening stage, but were unable to confirm these preliminary observations at follow-up [19].
  • The majority of cancer tissues (35/50), benign tissues (8/9) and all cancer adjacent normal tissues (20/20) released heat labile, NR6 transforming activity which coeluted from heparin with acidic FGF (aFGF) at 0.9-1.1 M NaCl and was neutralised by antibodies to aFGF [4].
  • The authors identified the abducent nerve with certainty in 96% of 3-D CISS sequences obtained in the axial and sagittal planes and in 94% obtained in the coronal plane [20].
  • Experimental data showed that CLF-1 and CLF-2, both carbohydrate-containing fractions, had different chromatographic patterns from excreted factor (EF), a polysaccharide antigen from Leishmania [21].
  • Ciprofloxacin t1/2, VSSF, CLF, and CLR in the matched CF subjects averaged 4.5 hours, 2.8 L/kg, 2.73 mL/min/kg and 5.7 mL/min/kg, respectively [22].

Physical interactions of CRLF1


Other interactions of CRLF1

  • The Australian case, however, had no pathogenic sequence variants in the CRLF1 gene, but was compound heterozygous for mutations in the CLCF1 gene on chromosome 11q13.3 (CISS2) [12].
  • One of the largest classes identified as upregulated PLAG1 targets consists of growth factors such as the insulin-like growth factor II and the cytokine-like factor 1 [24].

Analytical, diagnostic and therapeutic context of CRLF1

  • Western blot analysis of recombinant forms of hCLF-1 showed that the protein has the tendency to form covalently linked di- and tetramers [13].
  • Whereas mAb 806 displayed antitumor activity against NR6 xenografts, mAb 528 therapy was ineffective, suggesting that mAb 528 mediates its antitumor activity by disrupting interactions between the de2-7 and wild-type EGFR [25].
  • All persons receiving 720 ELISA units (El.U) of the CLF vaccine seroconverted after one dose [26].
  • CISS imaging and T2-weighted imaging were equally useful for monitoring postoperative changes in the sizes of ventricles or cysts and the presence of flow voids after third ventriculostomies [5].
  • CISS with SUZI showed increased efficiency in achieving fertilization and is a novel approach to studying individual sperm function in a sperm egg bioassay where gamete ratios are close to unity [27].


  1. Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component. Lelièvre, E., Plun-Favreau, H., Chevalier, S., Froger, J., Guillet, C., Elson, G.C., Gauchat, J.F., Gascan, H. J. Biol. Chem. (2001) [Pubmed]
  2. Resistance to nitric oxide-mediated apoptosis in HL-60 variant cells is associated with increased activities of Cu,Zn-superoxide dismutase and catalase. Yabuki, M., Kariya, S., Ishisaka, R., Yasuda, T., Yoshioka, T., Horton, A.A., Utsumi, K. Free Radic. Biol. Med. (1999) [Pubmed]
  3. Controlled clinical comparison of bioMérieux VITAL and BACTEC NR-660 blood culture systems for detection of bacteremia and fungemia in adults. Wilson, M.L., Mirrett, S., McDonald, L.C., Weinstein, M.P., Fune, J., Reller, L.B. J. Clin. Microbiol. (1999) [Pubmed]
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  5. Value of constructive interference in steady-state three-dimensional, Fourier transformation magnetic resonance imaging for the neuroendoscopic treatment of hydrocephalus and intracranial cysts. Aleman, J., Jokura, H., Higano, S., Akabane, A., Shirane, R., Yoshimoto, T. Neurosurgery (2001) [Pubmed]
  6. Use of the Coping Inventory for Stressful Situations in a clinically depressed sample: factor structure, personality correlates, and prediction of distress. McWilliams, L.A., Cox, B.J., Enns, M.W. Journal of clinical psychology. (2003) [Pubmed]
  7. Silencing by plant Polycomb-group genes requires dispersed trimethylation of histone H3 at lysine 27. Schubert, D., Primavesi, L., Bishopp, A., Roberts, G., Doonan, J., Jenuwein, T., Goodrich, J. EMBO J. (2006) [Pubmed]
  8. An ancient role for a prokineticin domain in invertebrate hematopoiesis. Söderhäll, I., Kim, Y.A., Jiravanichpaisal, P., Lee, S.Y., Söderhäll, K. J. Immunol. (2005) [Pubmed]
  9. Two different contact sites are recruited by cardiotrophin-like cytokine (CLC) to generate the CLC/CLF and CLC/sCNTFRalpha composite cytokines. Perret, D., Guillet, C., Elson, G., Froger, J., Plun-Favreau, H., Rousseau, F., Chabbert, M., Gauchat, J.F., Gascan, H. J. Biol. Chem. (2004) [Pubmed]
  10. MRI of inner ear and facial nerve pathology using 3D MP-RAGE and 3D CISS sequences. Held, P., Fellner, C., Fellner, F., Seitz, J., Graf, S., Hilbert, M., Strutz, J. The British journal of radiology. (1997) [Pubmed]
  11. Evaluation of multiple regimens in leprosy. Ramu, G., Sreevatsa, n.u.l.l., Sengupta, U., Desikan, K.V. Leprosy in India. (1981) [Pubmed]
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  13. Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family. Elson, G.C., Graber, P., Losberger, C., Herren, S., Gretener, D., Menoud, L.N., Wells, T.N., Kosco-Vilbois, M.H., Gauchat, J.F. J. Immunol. (1998) [Pubmed]
  14. Transformation mediated by the human HER-2 gene independent of the epidermal growth factor receptor. Chazin, V.R., Kaleko, M., Miller, A.D., Slamon, D.J. Oncogene (1992) [Pubmed]
  15. Isolation and expression analysis of petunia CURLY LEAF-like genes. Mayama, T., Ohtsubo, E., Tsuchimoto, S. Plant Cell Physiol. (2003) [Pubmed]
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  17. Familial complex chromosome rearrangement ascertained by in situ hybridisation. Fuster, C., Miguez, L., Miró, R., Rigola, M.A., Perez, A., Egozcue, J. J. Med. Genet. (1997) [Pubmed]
  18. Constructive interference in steady state-3DFT MR imaging of the inner ear and cerebellopontine angle. Casselman, J.W., Kuhweide, R., Deimling, M., Ampe, W., Dehaene, I., Meeus, L. AJNR. American journal of neuroradiology. (1993) [Pubmed]
  19. Haplotype-based association analysis of 56 functional candidate genes in the IBD6 locus on chromosome 19. Tello-Ruiz, M.K., Curley, C., DelMonte, T., Giallourakis, C., Kirby, A., Miller, K., Wild, G., Cohen, A., Langelier, D., Latiano, A., Wedemeyer, N., Lander, E., Schreiber, S., Annese, V., Daly, M.J., Rioux, J.D. Eur. J. Hum. Genet. (2006) [Pubmed]
  20. Detailed magnetic resonance imaging anatomy of the cisternal segment of the abducent nerve: Dorello's canal and neurovascular relationships and landmarks. Yousry, I., Camelio, S., Wiesmann, M., Schmid, U.D., Moriggl, B., Brückmann, H., Yousry, T.A. J. Neurosurg. (1999) [Pubmed]
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  25. The efficacy of epidermal growth factor receptor-specific antibodies against glioma xenografts is influenced by receptor levels, activation status, and heterodimerization. Johns, T.G., Perera, R.M., Vernes, S.C., Vitali, A.A., Cao, D.X., Cavenee, W.K., Scott, A.M., Furnari, F.B. Clin. Cancer Res. (2007) [Pubmed]
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  27. Computer image sperm selection as a novel approach to subzonal insemination in the human. Green, S., Fishel, S., Hall, J., Hunter, A., Fleming, S., Hobson, G., Roe, H., Dowell, K., Thornton, S., Klentzeris, L. Hum. Reprod. (1995) [Pubmed]
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