Description
Gremlin, also known as Drm, is a highly conserved 20.7-kDa, 184 amino acid glycoprotein part of the DAN family and is a cysteine knot-secreted protein. Skeletal cells synthesize bone morphogenetic proteins (BMPs) and BMP antagonists. And Gremlin is expressed in osteoblasts and opposes BMP effects on osteoblastic differentiation and function in vitro. Gremlin 1 (GREM 1) is known for its antagonistic reaction with BMPs in the TGF beta signaling pathway. This gene inhibits BMP-2, BMP-4, and BMP-7. Inhibition by grem 1 of BMPs in mice allow the expression of fibroblast growth factors (FGFs) 4 and 8 and Sonic hedgehog (SHH) which are necessary for proper limb development. Gremlin 1 may play an oncogenic role especially in carcinomas of the uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma. Over-expressed gremlin 1 functions by interaction with YWHAH (Its binding site for gremlin 1 was located between residues 61-80 and gremlin 1 binding site for YWHAH was found to be located between residues 1-67). Therefore, Gremlin 1 and its binding protein YWHAH could be good targets for developing diagnostic and therapeutic strategies against human cancers