Role of COP9 signalosome subunit 3 (CSN3) phosphorylation in integrin-mediated cardiac hypertrophy
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Authors
Teh, Denise N. E.
Issue Date
2010
Type
Thesis
Language
en_US
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Abstract
Integrins are involved in various aspects of cell regulation, signaling, and growth and
have been shown to react to environmental stimuli such as mechanical stress in cardiac
myocytes. These integrin-mediated reactions may be linked to the upregulation of
hypertrophic genes that result in cardiac hypertrophy, which is the focus of our lab. CSN
is a highly conserved complex involved in cell regulation and a critical component to cell
differentiation. Previous research has shown that the third subunit of the COP9
signalosome (CSN3) complex binds specifically to ß1D integrin, an isoform that is
predominant in adult striated muscle. CSN3 is phosphorylated on serine residues 410, 421
and 423; however the role of these phosphorylation sites remains to be determined.
Therefore, we hypothesize that phosphorylation at one or a combination of these sites
results in the physical disassociation of CSN3 from ß1D integrin upon integrin activation.
To test this hypothesis, CSN3 serine residues 410, 421 and 423 were mutated to either
Alanine (to prevent phosphorylation) or Aspartic Acid (to mimic phosphorylation). The
following techniques were utilized in this experiment: polymerase chain reaction (PCR),
gel electrophoresis and DNA purification. All constructs were confirmed to contain both
the pShuttle-IRES-hrGFP-1 vector and the CSN3 gene with the desired mutations via
DNA sequencing.
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In Copyright(All Rights Reserved)