20.109 MOD3 Research Proposal

Maryelise Cieslewicz
Kyle Atmore

"Peroxiredoxin 1 PDB image"

Topic

• Peroxiredoxin inhibition to facilitate cancer therapy

Topic Background

• Prx's are mostly found in the cytosol (also found in mitochondria, chloroplasts, and peroxisomes).
• Prx's exhibit antioxidant behavior through peroxidase activity, reducing organic hydroperoxides.
• Many cancer cells and tissues show increased expression levels of both Prx1 and Prx2.
• Expression of both Prx's in cancer cells has been associated with increased resistance to standard cancer treatments.
  • Prx1 expression may be used as a predictive indicator of relative risk of death or patient survival among cancer patients.
• Prx1 may be useful as a new therapeutic target in cancer treatments.

Research Ideas

• A specific cysteine residue is important for the Prx function. This cysteine could be modified in vivo to inactivate the enzyme. Cancer cell response to therapeutics could be measured for cells with and without the modifications.
• For overall cancer treatment, cells with increased expression levels of Prx1 could be targeted with therapies that inhibited Prx1 expression.

Publications

1. "Up-regulation of peroxiredoxin 1 in lung cancer and its implication as a prognostic and therapeutic target."[1]
2. "Structure, mechanism and regulation of peroxiredoxins."[2]
3. "Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate."[3]
4. "Identification of tumor antigens that elicit a humoral immune response in breast cancer patients' sera by serological proteome analysis (SERPA)"[4]
5. "Taenia solium: antioxidant metabolism enzymes as targets for cestocidal drugs and vaccines."[5]
6. "Presence of cytosolic peroxiredoxin 2 in the erythrocyte membrane of patients with hereditary spherocytosis." [6]
7. "Peroxiredoxins, a novel protein family in lung cancer"

[7]

Web Pages

1. Wikipedia - [8]