Differential effects of Ras signaling through NFkappaB on skeletal myogenesis

Oncogene
N MitinE J Taparowsky

Abstract

Oncogenic Ras (H-Ras G12V) inhibits skeletal myogenesis through multiple signaling pathways. Previously, we demonstrated that the major downstream effectors of Ras (i.e., MEK/MAPK, RalGDS and Rac/Rho) play a minor, if any, role in the differentiation-defective phenotype of Ras myoblasts. Recently, NFkappaB, another Ras signaling target, has been shown to inhibit myogenesis presumably by stimulating cyclin D1 accumulation and cell cycle progression. In this study, we address the involvement of NFkappaB activation in the Ras-induced inhibition of myogenesis. Using H-Ras G12V and three G12V effector-loop variants, we detect high levels of NFkappaB transcriptional activity in C3H10T1/2-MyoD cells treated with differentiation medium. Myogenesis is blocked by all Ras proteins tested, yet only in the case of H-Ras G12V are cyclin D1 levels increased and cell cycle progression maintained. Expression of IkappaBalpha SR, an inhibitor of NFkappaB, does not reverse the differentiation-defective phenotype of Ras expressing cultures, but does induce differentiation in cultures treated with tumor necrosis factor (TNFalpha) or in cultures expressing the RelA/p65 subunit of NFkappaB. These data confirm that NFkappaB is a target of Ras and sugge...Continue Reading

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Citations

Jun 26, 2003·Journal of Biomedical Science·Kuo-Chin HuangWan-Wan Lin
Jun 25, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Hong LiAshok Kumar
Jan 1, 2003·Seminars in Cancer Biology·Sharon Amit, Yinon Ben-Neriah
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Apr 13, 2021·Frontiers in Physiology·Qianghua XiaYongjie Wei
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Sep 22, 2021·Animal Science Journal = Nihon Chikusan Gakkaihō·Xiaoli XuJiaxue Cao
Feb 12, 2020·Molecular Therapy. Nucleic Acids·Binglin YueHong Chen

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