Osteogenic protein-1 regulates L1 and neural cell adhesion molecule gene expression in neural cells.
Osteogenic protein-1 (OP-1) is a member of the TGF-beta superfamily that is expressed in the nervous system. We recently showed that human recombinant osteogenic protein-1 (hOP-1) strongly promotes the aggregation of dividing neuroblastoma x glioma hybrid NG108-15 cells, in part by inducing the major isoforms of the neural cell adhesion molecule (N-CAM) (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 10326-10330). Here we show that hOP-1 induces L1 expression approximately 6-fold in NG108-15 cells without changing the levels of N-cadherin, neurofilament 200, Thy-1, tau, and G alpha s. OP-1 induction of L1 and N-CAM was unassociated with changes in cell proliferation and was not reproduced by cellular differentiation. The increased adhesiveness of hOP-1-treated NG108-15 cells could be inhibited in part by Fab fragments of an anti-L1 polyclonal antiserum. L1 and N-CAM expression first increased 12-18 h after hOP-1 treatment, reached a maximum after 2-3 days, persisted for up to 5 days, and returned to control levels 3 days after hOP-1 withdrawal. The increases in L1 and N-CAM protein levels were preceded or accompanied by large increases in the abundance of L1 and all detectable N-CAM mRNAs. Actinomycin D prevented the induction by hOP-1 of L1 and N-CAM mRNAs, suggesting that hOP-1 regulates immunoglobulin CAM gene transcription. OP-1 is the first described growth factor that regulates both N-CAM and L1 gene expression.
Perides
G
G
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
Hu
G
G
Rueger
D C
DC
Charness
M E
ME
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002135:Calcium-Binding Proteins / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D039841:Leukocyte L1 Antigen Complex; D016501:Neurites; D011498:Protein Precursors / Q000502:physiology; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D039841:Leukocyte L1 Antigen Complex; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013755:Tetradecanoylphorbol Acetate