Alternative titles; symbols
HGNC Approved Gene Symbol: CYTL1
Cytogenetic location: 4p16.2 Genomic coordinates (GRCh38) : 4:5,014,586-5,019,458 (from NCBI)
CYTL1 is a cytokine-like protein specifically expressed in bone marrow and cord blood mononuclear cells that bear the CD34 (142230) surface marker (Liu et al., 2000).
Using representational difference analysis-based subtraction, Liu et al. (2000) identified CYTL1, which they called C17, by its expression in CD34-positive but not CD34-negative hematopoietic cells. They obtained an EST clone containing C17 that originated from a 9-week whole embryo. The deduced 136-amino acid protein has a calculated molecular mass of 17.2 kD. C17 contains an N-terminal secretory signal peptide and 4 alpha helices, a characteristic of hematopoietic cytokines and interleukins. Northern blot analysis detected a 1.0-kb transcript in adult bone marrow-derived CD34-positive cells. C17 expressed by transfected 293T cells migrated with an apparent molecular mass of about 26 kD on SDS/PAGE gels. A minor protein seen only in transfected cells migrated with an apparent molecular mass of about 40 kD. Digestion with glycosidases indicated that the unexpectedly high molecular mass was not due to glycosylation.
Using quantitative RT-PCR, Kim et al. (2007) detected highest expression of mouse Cytl1 in cartilage, with lower expression in lung, heart, trachea, and testis, and little to no expression in eye, brain, kidney, muscle, spleen, and liver. Expression was also detected in primary culture mouse chondrocytes, but not in chondrosarcoma or chondroprogenitor cell lines. RT-PCR of developing mouse forelimb buds revealed that expression of Cytl1 occurred prior to that of collagen IIB (COL2A1; 120140) and peaked at 14.5 days postcoitum. It was not expressed in hypertrophic chondrocytes. Cytl1 was secreted from cultured mouse chondrocytes and had an apparent molecular mass of about 6.4 kD by SDS-PAGE. Database analysis identified CYTL1 orthologs in several vertebrate species, but not in invertebrates, suggesting that CYTL1 originated early in vertebrate evolution.
Liu et al. (2000) determined that expression of C17 mRNA increased in cultured adult bone marrow-derived CD34-positive cells exposed to cytokines that favor maintenance of stem cells. Expression decreased when cells were exposed to hematopoietic colony-stimulating factors that stimulate cell differentiation.
Kim et al. (2007) found that overexpression of Cytl1 or application of exogenous recombinant mouse Cytl1 to mouse limb bud mesenchymal micromass cultures induced chondrogenic differentiation, as shown by synthesis of sulfated proteoglycans and expression of collagen IIB. Exogenous Cytl1 enhanced transcriptional activity of Sox9 (608160) and induced Igf1 (147440) expression, both of which can induce chondrogenic differentiation. Inhibition of Erk (see 601795) enhanced and inhibition of p38 MAP kinase (MAPK14; 600289) or PKC-alpha (see 176960) blocked Cytl1-induced collagen IIB expression and accumulation of sulfated proteoglycan.
Using quantitative RT-PCR, Jeon et al. (2011) found significant downregulation of CYTL1 in human osteoarthritis (see 165720).
By radiation hybrid analysis and genomic sequence analysis, Liu et al. (2000) mapped the C17 gene to chromosome 4p16-p15.
Jeon et al. (2011) found that Cytl1 -/- mice were viable and showed normal postnatal growth and development of lung, heart, and long bones. Cytl1 -/- mice exhibited normal cartilage development and endochondral ossification. Chondrogenesis of Cytl1 -/- mesenchymal cells induced by micromass cultures was normal. Cytl1 expression was reduced in a mouse model of osteoarthritis, and deletion of Cytl1 enhanced osteoarthritis cartilage destruction. Jeon et al. (2011) concluded that CYTL1 is not essential for induction of chondrogenesis, but that it may be required for maintenance of cartilage homeostasis.
Jeon, J., Oh, H., Lee, G., Ryu, J.-H., Rhee, J., Kim, J.-H., Chung, K.-H., Song, W.-K., Chun, C.-H., Chun, J.-S. Cytokine-like 1 knock-out mice (Cytl1-/-) show normal cartilage and bone development but exhibit augmented osteoarthritic cartilage destruction. J. Biol. Chem. 286: 27206-27213, 2011. [PubMed: 21652695] [Full Text: https://doi.org/10.1074/jbc.M111.218065]
Kim, J.-S., Ryoo, Z. Y., Chun, J.-S. Cytokine-like 1 (CYTL1) regulates the chondrogenesis of mesenchymal cells. J. Biol. Chem. 282: 29359-29367, 2007. [PubMed: 17644814] [Full Text: https://doi.org/10.1074/jbc.M700965200]
Liu, X., Rapp, N., Deans, R., Cheng, L. Molecular cloning and chromosomal mapping of a candidate cytokine gene selectively expressed in human CD34+ cells. Genomics 65: 283-292, 2000. [PubMed: 10857752] [Full Text: https://doi.org/10.1006/geno.2000.6170]