| Summary: | Doctor of Philosophy === Department of Biology === Alexander Beeser === Large-scale genomic approaches have demonstrated many atypical dual specificity
phosphatases (DUSPs) are differentially expressed or mutated in cancer. DUSPs are proteins
predicted to have the ability to dephosphorylate Ser/Thr and Tyr residues, and the atypical DUSP
subgroup contains at least 16 members with diverse substrates that include proteins, nucleic
acids, and sugars, and some of the atypical DUSPs function in the cell not as phosphatases but as
scaffolds in signal transduction pathways. Of the atypical DUSPs, DUSP12 is one of the most
evolutionarily conserved with homologs found in organisms ranging from yeast to humans.
DUSP12 is of particular interest as it has been identified to be one of only two candidate genes
for the target of a genetic amplification found in liposarcomas. Furthermore, DUSP12 may be an
oncogene in that over-expression of dusp12 in cell culture promotes apoptosis resistance, cell
motility, and the up-regulation of two established oncogenes, the hepatocyte growth factor
receptor (c-met) and integrin alpha 1 (itga1). Additionally, DUSP12 may protect from apoptosis
by functioning as a regulator of stress-induced translation repression and stress granule formation
that may be due to its interaction with the DEAD Box RNA Helicase, DDX3.
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