Regulating the availability of transforming growth factor ß1 in B104 neuroblastoma cells.
Transforming growth factor (TGF) beta1 is a key player in early brain development, hence, its availability (i.e., synthesis and release) affects neuronogenesis. TGFbeta1 moves proliferating cells out of the cell cycle and promotes their subsequent migration. The present study tested the hypothesis that neural progenitors self-regulate TGFbeta1. B104 neuroblastoma cells which can grow in the absence of serum or growth factors were used in systematic studies of transcription, translation, release, and activation. These studies relied on quantitative enzyme-linked immunosorbent assays and real-time polymerase chain reactions. TGFbeta1 positively upregulated its own intracellular expression and promoted increased release of TGFbeta1 from cells. The induction of TGFbeta1 was independent of a change in transcription, but it depended on cycloheximide-inhibited translation. Signaling mediated by downstream Smad2/3 through the TGFbeta receptors and intracellular protein transport were also required for release of TGFbeta1 from B104 cells. Thus, TGFbeta1 production and release were mediated through a feed-forward mechanism and were pivotally regulated at the level of translation. These activities appear to be key for the role of TGFbeta1 in the proliferation and migration of young neurons.
Lindke
Amanda L
AL
Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, Syracuse NY 13210, USA.
Middleton
Frank A
FA
Miller
Michael W
MW
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D014176:Protein Biosynthesis; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1