CLCF1 explained

Cardiotrophin-like cytokine factor 1 (CLCF1), also known as Novel Neurotrophin-1 (NNT-1) or B cell-stimulating factor-3 (BSF-3), is a protein that in humans is encoded by the CLCF1 gene.^[1]

Function

CLCF1 is a cytokine. It induces tyrosine phosphorylation of the IL-6 receptor common subunit glycoprotein 130 (gp130), leukemia inhibitory factor receptor beta, and the transcription factor STAT3. It has been implicated in the induction of IL-1 (via induction of corticosterone and IL-6) and serum amyloid A, and in B cell hyperplasia. CLCF1 is capable of B cell activation via gp130 receptor stimulation.^[2]

Structure

CLCF1 is a cytokine belonging to the interleukin-6 (IL6) family. It is a secreted protein, found predominantly in lymph nodes and spleen, and contains 225 amino acids with a molecular mass of 22 kDa in its mature form. IL6 family members share similarity in gene structure and have a 4-helix bundle in their protein structure. CLCF1 is closely related to other proteins called cardiotrophin-1 and ciliary neurotrophic factor.

Further reading

• Shi Y, Wang W, Yourey PA . Computational EST database analysis identifies a novel member of the neuropoietic cytokine family. . Biochem. Biophys. Res. Commun. . 262 . 1 . 132–8 . 1999 . 10448081 . 10.1006/bbrc.1999.1181 . etal.
• Senaldi G, Varnum BC, Sarmiento U . Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. . Proc. Natl. Acad. Sci. U.S.A. . 96 . 20 . 11458–63 . 1999 . 10500198 . 10.1073/pnas.96.20.11458 . 18055 . 1999PNAS...9611458S . etal. free .
• Elson GC, Lelièvre E, Guillet C . CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. . Nat. Neurosci. . 3 . 9 . 867–72 . 2000 . 10966616 . 10.1038/78765 . 25766998 . etal.
• Plun-Favreau H, Elson G, Chabbert M . The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine. . EMBO J. . 20 . 7 . 1692–703 . 2001 . 11285233 . 10.1093/emboj/20.7.1692 . 145510 . etal.
• Lelièvre E, Plun-Favreau H, Chevalier S . 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. . J. Biol. Chem. . 276 . 25 . 22476–84 . 2001 . 11294841 . 10.1074/jbc.M101681200 . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Auernhammer CJ, Isele NB, Kopp FB . Novel neurotrophin-1/B cell-stimulating factor-3 (cardiotrophin-like cytokine) stimulates corticotroph function via a signal transducer and activator of transcription-dependent mechanism negatively regulated by suppressor of cytokine signaling-3. . Endocrinology . 144 . 4 . 1202–10 . 2003 . 12639901 . 10.1210/en.2002-220933 . etal. free .
• Burger R, Bakker F, Guenther A . Functional significance of novel neurotrophin-1/B cell-stimulating factor-3 (cardiotrophin-like cytokine) for human myeloma cell growth and survival. . Br. J. Haematol. . 123 . 5 . 869–78 . 2004 . 14632778 . 10.1046/j.1365-2141.2003.04686.x . 28659799 . etal. free .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Rousseau F, Gauchat JF, McLeod JG . Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient. . Proc. Natl. Acad. Sci. U.S.A. . 103 . 26 . 10068–73 . 2006 . 16782820 . 10.1073/pnas.0509598103 . 1502507 . 2006PNAS..10310068R . etal. free .
• Dagoneau N, Bellais S, Blanchet P . Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes. . Am. J. Hum. Genet. . 80 . 5 . 966–70 . 2007 . 17436251 . 10.1086/513608 . 1852726 . etal.

External links

• GeneReviews/NCBI/NIH/UW entry on Cold-Induced Sweating Syndrome including Crisponi Syndrome
• OMIM enries on Cold-Induced Sweating Syndrome including Crisponi Syndrome

Notes and References

1. Web site: Entrez Gene: CLCF1 cardiotrophin-like cytokine factor 1.
2. Senaldi G, Varnum BC, Sarmiento U, Starnes C, Lile J, Scully S, Guo J, Elliott G, McNinch J, Shaklee CL, Freeman D, Manu F, Simonet WS, Boone T, Chang MS . Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family . Proc. Natl. Acad. Sci. U.S.A. . 96 . 20 . 11458–63 . September 1999 . 10500198 . 18055 . 10.1073/pnas.96.20.11458. 1999PNAS...9611458S . free .