Adam Duxfield

• BSc (Hons) Biomedical Sciences
• The role of p52/p100 NF-κB2 Serine 222 phosphorylation in senescence and cancer

My project was based on the NF-kB2 (p100/p52) transcription factor, an effector of the non-canonical NF-kB pathway, an important regulator of the immune system that becomes activated in many forms of cancer. I investigated the role of phosphorylation, the addition of a phosphate group, at the amino acid serine 222 (S222) of p100/p52. Phosphorylation at this site affects p52 DNA binding and p52 dependant cell growth. I also investigated the kinase (enzyme) responsible for p100/p52 S222 phosphorylation by using a series of different kinase inhibitors in the U2OS cancer cell line. Furthermore, I also investigated p100/p52 S222 phosphorylation using protein extracts provided by a collaborating laboratory from patients with Chronic Lymphocytic Leukemia (CLL). My data demonstrated that candidate kinases, ERK1/2, do not phosphorylate p100/p52 at S222. I also confirmed that p100/p52 S222 phosphorylation changes as cells from CLL patients start to proliferate suggesting an important regulatory role in this disease.

Funding source: Newcastle University

Supervisor: Professor Neil Perkins