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Theses/Dissertations

2013

Inflammation

Cell Biology

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The Role Of Tipe2 In The Regulation Of Inflammation And Tumorigenesis, Derek Johnson Jan 2013

The Role Of Tipe2 In The Regulation Of Inflammation And Tumorigenesis, Derek Johnson

Publicly Accessible Penn Dissertations

TIPE2 is a recently discovered regulator of immunity and inflammation. Here we describe a new function of TIPE2 in the regulation of Ras signaling and Tumorigenesis. By using various stimuli and inhibitors in T Cells and macrophages we discovered that TIPE2 is regulated at both the message and protein level by inflammatory stimuli. TIPE2 mRNA is regulated in the short to intermediate term by an NF-Kappa B induced micro RNA, and TIPE2 is also ubiquitylated and degraded, possibly by SCF-Beta TRCP. Mechanistically TIPE2 interacts with and inhibits the Ras-interacting domain of the RalGDS family of Ras effectors, leading to a ...