Protein-protein interaction between multi-functional protein CAD and protein phosphastase 1 (PP1)

<p>Uncontrolled cell proliferation, a hallmark of cancer, is associated with activation of CAD, a multifunctional protein that catalyzes the first three steps in pyrimidine biosynthesis. The cell cycle dependent regulation of pyrimidine biosynthesis is a consequence of sequential phosphorylation of CAD Thr-456 and Ser-1406 by the MAP kinase and PKA cascades, respectively. The mechanism that controls the timing of these events is not well understood. Our hypothesis is that timing of the activation and nucleocytoplasmic dynamics of CAD is controlled by signaling complexes with kinases and phosphatases. Interestingly, a consensus sequence for PP1 targeting proteins is located immediately adjacent to Thr-456. Peptides were synthesized corresponding to residues 444-460 of CAD that encompasses both the PP1 consensus sequence and Thr-456 as well as two mutant peptides in which Thr-456 was replaced with Ala or Asp. The wild type peptide and Ala mutant were able to bind to PP1 while the Asp mutant which, mimics phosphorylated CAD, does not.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Open Access Thesis

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2013

Author dc:creator

• Mhaskar, Meenal

Contributors dc:contributor

• Hedeel Evans, Ph.D., Chair
• Deborah Heyl-Clegg, Ph.D.
• Ruth Ann Armitage, Ph.D.

• Cell poliferation
• cancer
• phosphorylation
• Chemistry

Repository record dc:identifier

https://commons.emich.edu/theses/558

OAI identifier oai:identifier

oai:commons.emich.edu:theses-1931