Skeletal Muscle Differentiation

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Skeletal muscle proliferation and differentiation are closely coordinated and highly regulated processes. It is marked by quite an impressive change in gene expression in terms of amplitude of the expression and the number of the genes being regulated simultaneously. For instance, hundreds of cell cycle effector genes go from highly expressed to permanently silenced as myoblasts differentiate into myotubes [12]. Cell cycle progression (proliferation), arrest/withdrawal and differentiation are three important steps of skeletal muscle development. Cell cycle arrest is critical step for muscle differentiation. Two of the most important proteins involved in cell cycle machinery are cyclins and cyclin-dependent kinases (CDKs). Different Cyclins/CDKs complexes formed during different phases of cell cycles are able to specifically phosphorylate distinct set of target proteins.…show more content…
In mammals, Cyclin D and E mediate the progression through G1/S phases [13]. Mitotic Cyclins A and B mediate the progression through the S/G2/M phases. D-type Cyclins are short lived proteins whose synthesis and assembly with CDK4 or CDK6 is dependent on mitogenic signaling [14]. Cyclin D/Cdk complexes are active as long as mitogenic stimulation continues. Cyclin D drives cells cycle progression through phosphorylation of critical cellular substrates. In addition, D type cyclins play a kinase independent role by sequestering CDK inhibitors p27kip1 and p21cip1 [13]. Cyclin E protein level peaks at G1/S progression, followed by increase in Cyclin A levels in S-phase. CDK2 can form complexes with both Cyclin A and E, whereas CDK1 can only form complex with Cyclin A. Increase in Cyclin B level results into induction in level of CDK1 at G2/M phase. The resultant fluctuation in expression of Cyclins and oscillation of CDKs activities form the basis of coordinated cell cycle progression (reviewed in

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