CKLFSF2B, a Developmentally Regulated Testicular Protein, Regulates Steroidogenesis
Presentation Number: SUN 259
Date of Presentation: April 2nd, 2017
Sudeep Kumar*1 and Keesook Lee2
1School of Biological Sciences and Biotechnology, Chonnam National University, Gwangju, Korea, Republic of (South), 2School of Biological Sciences and Biotechnology,Chonnam National University, Gwangju, Korea, Republic of (South)
Chemokine-like factor superfamily (CKLFSF) is a protein family that serves as functional bridge between chemokines and the members of transmembrane 4 superfamily (TM4SF). There are nine genes, CKLF and CKLFSF1-8, which encode CKLFSF proteins in human. Human CKLFSF2 is detected in spermatogonia and secreted into the tissue fluid of the testis, suggesting its role in the development of germ cells and other testicular function. In course of evolution, CKLFSF2 has evolved as two isoforms namely CKLFSF2A and CKLFSF2B in mouse. CKLFSF2A, also known as androgen receptor co-repressor, is expressed in the testis and has a role in testicular steroidogenesis. In this study, we investigated the expression of CKLFSF2B and its function and regulation in the testis. Cklfsf2b is developmentally regulated and highly expressed in the testis. It is expressed only in Leydig cells at prepubertal stages, whereas it is highly expressed in haploid germ cells and Leydig cells in adult testis. CKLFSF2B is naturally processed inside cells at its C-terminus to yield a smaller protein of ~20 KDa compared to the full size of ~25 KDa. The expression of Cklfsf2b is regulated by GATA-1 and CREB protein through binding to their respective binding elements present within the 2Kb upstream promoter sequence. The nur77 promoter activity is directly repressed by overexpression of CKLFSF2B, which consequently represses the promoter activity of steroidogenic genes such as P450c17, 3β-HSD and StAR in MA-10 Leydig cells. Adenovirus-mediated overexpression of CKLFSF2B in primary Leydig cells isolated from adult mice clearly showed the repression of steroidogenic gene expression and consequently testosterone production. Moreover, intratesticular injection of CKLFSF2B-expressing adenovirus in adult mice ascertained its repressive effect on testicular steroidogenesis when compared to only GFP-expressing adenovirus injected control. All together, these findings suggest that CKLFSF2B is likely involved in the development and function of germ cells and other testicular cells, and regulates testosterone production by fine-tuning the steroidogenesis in the testis.
Nothing to Disclose: SK, KL