Paper Type

Master's Thesis


College of Arts and Sciences

Degree Name

Master of Science in Biology (MS)



NACO controlled Corporate Body

University of North Florida. Department of Biology

First Advisor

Dr. David Waddell

Second Advisor

Dr. Frank Smith

Third Advisor

Dr. Joy Wolfram


Fam83d and Dupd1 have been identified as novel genes in skeletal muscle that are upregulated in response to neurogenic atrophy in a mouse model. qPCR analysis reveaed both genes are expressed in skeletal muscle with Fam83d expression being highest during myoblast proliferation, while Dupd1 expression is highest during myotube differentiation. Overexpression of either protein results in inhibition of proper muscle cell differentiation as evidenced by repression of both myosin heavy chain and myogenin expression. Characterization of transcriptional activity revealed both genes are modulated by myogenic regulatory factors and additionally, Dupd1 expression is enhanced by dexamethasone treatment. Assessment of subcellular localization revealed that Fam83d localizes in a punctate manner in the cytoplasm, while the expression of Dupd1 showed ubiquitous distribution throughout the cell. To assess function, Fam83d or Dupd1 were ectopically overexpressed in cultured muscle cells. Overexpression of Fam83d resulted in significant repression of phosphorylated ERK and AKT. Interestingly, inhibition of the 26S proteasome and the MAP kinase signaling pathway both resulted in stabilization of Fam83d during muscle cell differentiation. Finally, Fam83d has a putative phospholipase D-like domain that appears to be necessary for destabilizing casein kinase Iα and inhibiting ERK phosphorylation in cultured myoblasts. Overexpression of Dupd1 resulted in significant repression of phosphorylated ERK and AMPK. Additionally, Dupd1 overexpression resulted in dramatic increases in GR protein as well as phosphorylated GR, while attenuating activity of a GRE reporter gene. The discovery that Fam83d and Dupd1 are expressed in skeletal muscle combined with the observation that they are induced in response to neurogenic atrophy helps further our understanding of the molecular and cellular events of skeletal muscle wasting