The expression of CKLFSF2B is regulated by GATA1 and CREB in the Leydig cells, which modulates testicular steroidogenesis

Publication date: Available online 12 October 2018Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory MechanismsAuthor(s): Sudeep Kumar, Hana Kang, Eunsook Park, Hee-Sae Park, Keesook LeeAbstractCKLFSF is a protein family that serves as a functional bridge between chemokines and members of the transmembrane 4 superfamily (TM4SF). In the course of evolution, CKLFSF2 has evolved as two isoforms, namely CKLFSF2A and CKLFSF2B, in mice. CKLFSF2A, also known as CMTM2A and ARR19, is expressed in the testis and is important for testicular steroidogenesis. CKLFSF2B is also known to be highly expressed in the testis. In the prepubertal stage, CKLFSF2B is expressed only in Leydig cells, but it is highly expressed in haploid germ cells and Leydig cells in adult testis. CKLFSF2B is naturally processed inside the cell at its C-terminus to yield smaller proteins compared to its theoretical size of ≈25 kDa. The Cklfsf2b gene is regulated by GATA-1 and CREB protein, binding to their respective binding elements present in the 2-kb upstream promoter sequence. In addition, the overexpression of CKLFSF2B inhibited the activity of the nur77 promoter, which consequently represses the promoter activity of Nur77-target 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 shows a repression of steroidogenic gene expression and consequently testosterone production. More...

Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - October 12, 2018 Category: Genetics & Stem Cells Source Type: research