Lab Website: https://habelhah.lab.uiowa.edu/

The role of TRAF2 phosphorylation in NF-κB activation and cancer cell resistance to apoptosis

The NF-κB transcription factors play critical roles in regulating inflammation, the immune response, cell proliferation and survival. Abnormal NF-κB activation has been observed in various inflammatory diseases and many types of cancers. TRAF2 is a prototypical member of the TRAF family, and transduces signals that emanate from several members of the TNF receptor superfamily, resulting in activation of the NF-κB pathway. By classical phosphopeptide mapping approaches, we mapped two phosphorylation sites (Ser-11 and Ser-55) on the N-terminal region of TRAF2, and discovered that TRAF2 phosphorylation increases both the basal and inducible NF-κB activity. Western blot analysis revealed that TRAF2 is constitutively phosphorylated in some cancer cell lines as well as in some human tumor tissues, suggesting that TRAF2 phosphorylation is one of the events responsible for the elevation of basal NF-κB activity in cancer cells. Recently, we found that endoplasmic reticulum (ER) and oxidative stresses also strongly induce TRAF2 phosphorylation at both Ser-11 and Ser-55 sites, and that such TRAF2 phosphorylation plays an essential role in cell survival in the context of chronic ER and oxidative stresses. Currently, we are characterizing the molecular mechanisms underlying the regulation of TRAF2 phosphorylation and exploring its pathophysiological significance in TNFα- and stress-induced NF-κB activation and cancer cell resistance to apoptosis. Our studies will advance our understanding of how cancer cells adapt to chronic cellular stresses.

PubMed link

Department/Program Affiliations:
Molecular Medicine
MSTP
Pathology