Determining the function of nuclear Bmp4

Abstract

Bone morphogenetic protein 4 (Bmp4) is a well known growth factor that regulates gene expression through the SMAD signaling pathway. Bmp4 is involved in many developmental processes and has been identified as an important factor in several cancers, including melanoma, ovarian cancer, and colon cancer. Surprisingly, Madoz‐Gurpide et al. (2006) observed Bmp4 in the nuclei of a minor percentage of cells in colon cancer tissues. In addition, our lab has recently discovered a nuclear variant of Bmp2 (nBmp2), the TGF‐β family member most closely related to Bmp4. These observations led us to hypothesize that a nuclear variant of Bmp4 (nBmp4) also exists. Preliminary analyses have been performed that verified nuclear localization of Bmp4 in several cancer cell lines. Subsequent analyses suggest that nBmp4 is translated from an alternative start codon downstream of the signal peptide sequence, which allows a bipartite nuclear localization signal to direct translocation of nBmp4 to the nucleus. In an effort to determine the function of nBmp4, a yeast two‐hybrid screen was performed using a cDNA library from MCF‐7 breast cancer cells. Several proteins were identified as potential interacting partners. These interacting proteins suggest a role for nBmp4 in protein degradation, reactive oxygen species modulation, and apoptosis. Research supported by NIH grant AR48839 and the Brigham Young University Cancer Research Center.