Media type: E-Article Title: Opposite functions of Jun‐B and c‐jun in growth regulation and neuronal differentiation Contributor: Schlingensiepen, Karl‐Hermann; Schlingensiepen, Reimar; Kunst, Mechthild; Klinger, Ingrid; Gerdes, Wilhelm; Seifert, Wilfried; Brysch, Wolfgang imprint: Wiley, 1993 Published in: Developmental Genetics Language: English DOI: 10.1002/dvg.1020140408 ISSN: 0192-253X; 1520-6408 Keywords: Cell Biology ; Developmental Biology ; Genetics Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>Induction of the <jats:italic>jun</jats:italic>‐<jats:italic>B</jats:italic> and/or <jats:italic>c</jats:italic>‐<jats:italic>jun</jats:italic> transcription factors is part of the immediate early response to diverse stimuli that induce alterations in cellular programs. While <jats:italic>c‐jun</jats:italic> is a protooncogene whose expression is required for induction of cell proliferation, <jats:italic>jun‐B</jats:italic> has recently been found to be induced by stimuli inducing differentiation in various cell lines. Furthermore, its expression is largely restricted to differentiating cells during embryogenesis. To determine the functional significance of these findings, we used antisense phosphorothioate oligodeoxynucleotides to inhibit expression of the two genes in proliferating and neuronally differentiating cells. While selective inhibition of <jats:italic>c‐jun</jats:italic> expression reduced proliferation rates, inhibition of <jats:italic>jun‐B</jats:italic> protein synthesis markedly increased proliferation in 3T3 fibroblasts, human mammary carcinoma cells and PC‐12 pheochromocytoma cells, suggesting <jats:italic>jun‐B</jats:italic> involvement in negative growth control. Neuronal differentiation of PC‐12 cells induced by nerve growth factor (NGF) was prevented by inhibition of <jats:italic>jun‐B</jats:italic> protein synthesis. PC‐12 cells not only failed to grow neurites but also remained in the proliferative state. Furthermore, in cultured primary neurons from rat hippocampus, inhibition of <jats:italic>jun‐B</jats:italic> expression, again, markedly reduced morphological differentiation. Conversely, inhibition of <jats:italic>c‐jun</jats:italic> protein synthesis enhanced morphological differentiation of both primary neurons and PC‐12 tumor cells. Thus, <jats:italic>jun‐B</jats:italic> expression is required for neuronal differentiation and its balance with <jats:italic>c‐jun</jats:italic> activity is involved in regulating key steps in proliferation and differentiation processes. © 1993Wiley‐Liss, Inc.</jats:p>