Nuclear localization of GDF5

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 3732 Growth and differentiation factors (GDFs) are members of the transforming growth factor-beta (TGF-s) superfamily, and are involved in embryonic skeletal development and adult tissue homeostasis. Growth and differentiation factor-5 (GDF5, also known as cartilage-derived morphogenetic protein-1 (CDMP1) and bone morphogenetic protein-14 (BMP14)) plays an integral role in promoting osteogenesis and chondrogenesis and is involved in cellular proliferation. GDF5 has been traditionally categorized as an extracellular signaling protein that functions through a SMAD-dependent signaling pathway. Recent work in our laboratory, however, has demonstrated that two other members of the TGF-s superfamily, Bmp2 and Bmp4, exist as nuclear variants as well as conventional secreted growth factors. We examined GDF5 to see if it can also localize to the nucleus. Immunohistochemical staining with an antibody against GDF5 revealed that endogenous GDF5 is localized to the nuclei of both 10T1/2 mesenchymal cells and BALB/3T3 fibroblasts. Nuclear localization of GDF5 was dependent on a bipartite nuclear localization signal that overlaps the site at which GDF5 is cleaved to release the propeptide, suggesting that the nuclear variant of GDF5, like Bmp2 and Bmp4, is an uncleaved proprotein.