Nuclear localized BMP2 promotes cell cycle progression

Abstract

Nuclear localized bone morphogenetic protein 2 (nBMP2) is a recently discovered protein produced by alternative translation of the BMP2 transcript. We have detected strong nBMP2 expression in numerous immortalized and tumor cell lines, but not in primary cells, suggesting that nBMP2 overexpression is correlated with cell cycle dysregulation. The objective of this study was to determine the impact of nBMP2 on the cell cycle. To accomplish this aim, we overexpressed nBMP2 in cultured cells, stained the cells with propidium iodide, and analyzed cell cycle distribution by flow cytometry. We found that overexpression of nBMP2 in the immortalized human cell line HEK293 and in the colon cancer cell line HT‐29 increased the percentage of cells in S phase. A yeast two‐hybrid screen identified the SCF E3 ligase ROC‐1 as an nBMP2 binding partner. ROC‐1 targets several cell cycle inhibitors (including p21, p27, and p57) for degradation by the proteasome, suggesting that overexpression of nBMP2 could promote the cell cycle by increasing degradation of one or more cell cycle inhibitors. Together, these data suggest that nBMP2 is a potential oncoprotein. Funding provided by NIH #AR048839.