Lipin1 Regulates Skeletal Muscle Differentiation through Extracellular Signal-regulated Kinase (ERK) Activation and Cyclin D Complex-regulated Cell Cycle Withdrawal

• DOI: 10.1074/jbc.m115.686519
• Publication Date: 2015-08-22T00:09:44Z
• Authors: Weihua Jiang; Jing Zhu; Xun Zhuang; Xiping Zhang; Tao Luo; Karyn A. Esser; Hongmei Ren
• Keywords: Cyclin-dependent kinase 4

Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity nuclear transcriptional functions. Several mouse models of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children homozygous null mutations the LPIN1 gene suffer from rhabdomyolysis. However, underlying pathophysiologic mechanism is still poorly understood. In present study we examined whether contributes to regulating regeneration. We characterized time course regeneration lipin1-deficient fld mice after injury. found exhibited smaller regenerated fiber cross-sectional areas compared wild-type response Our results a series vitro experiments suggest up-regulated translocated nucleus during myoblast differentiation key role myogenesis by cytosolic activation ERK1/2 form complex downstream effector cyclin D3-mediated cell cycle withdrawal. Overall, our reveals previously unknown expands understanding cellular molecular mechanisms