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Investigating the Molecular Mechanisms Involved in Skeletal Muscle Development: NF-kappa B and Skeletal Myogenesis

Year: 2009
Type: article
Abstract: The NF-κB family of transcription factors has been implicated in regulating a number of cellular processes such as immune response, cell survival, cellular proliferation, and differentiation.This dissertation will focus on the involvement of NF-κB in cellular proliferation and differentiation.Studies support that NF-κB functions in cellular proliferation through the transcriptional regulation of cyclin D1, but whether such regulation is attributed to a single NF-κB subunit remains unclear.In chapter two we examine endogenous cyclin D1 levels during cell cycle re-entry in mouse embryonic fibroblasts (MEFs) lacking specific NF-κB signaling subunits.We demonstrate that each of these subunits is dispensable for regulating cyclin D1 transcription.However, we found that resulting cyclin D1 protein was severely reduced in MEFs lacking only RelA/p65.Cycloheximide treatment revealed that this regulation was due to an increase in protein turnover.Similarly downregulation of cyclin D1 protein, but not RNA, was observed in vivo in multiple tissues lacking p65.Co-immunoprecipitation analysis also showed that p65 and cyclin D1 were capable of interacting, thus providing a possible explanation for cyclin D1 protein stability.In addition, although the decrease in cyclin D1 in p65 -/-MEFs was concomitant with lower CDK4 activity during cell cycle re-entry, this was not sufficient to affect S phase progression.Nevertheless, similar decreases in cyclin D1 protein in primary p65 -/- myoblasts was adequate to accelerate cell cycle exit and myogenesis in these cells.just to walk past your bench.I can't wait to move on to the next phase of our life together as husband and wife.I love you with all my heart.
Language: English
Subfield: Cancer Research
Open Access status: green
OpenAlex ID: W2254607510
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