TNFAIP8 proteins transfer PI(4,5)P2, PI(3,4,5)P3 from cytosolic vesicles to plasma membrane

Stable Identifier
Reaction [transition]
Homo sapiens
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The tumor necrosis factor alpha-induced protein 8 family are all thought to be related to carcinogenesis (Lou & Liu 2011). TNFAIP8 and TNFAIP8L1 (aka TIPE1) may play roles in oncogenesis and TNFAIP8L2 (aka TIPE2) is an essential negative regulator of both innate and adaptive immunity and may play an important role in the development of inflammatory diseases. TNFAIP8L3 (aka TIPE3) is an important regulator of tumorigenesis through its activation of phospholipid signaling (Fayngerts et al. 2014). TNFAIP8 proteins are cytosolic proteins that contain a large hydrophobic cavity that is occupied by a phospholipid-like molecule. Although TNFAIP8 proteins can transport many phospholipids, they are thought to preferentially transport phosphoinositol-4,5-bisphosphate (PI(4,5)P2) and phosphoinositol-3,4,5-trisphosphate (PI(3,4,5)P3) from cytoplasmic vesicle membranes to the plasma membrane (Moniz & Vanhaesebroeck 2014, Cui et al. 2015). TNFAIP8L3 is highly expressed in most human carcinoma cell lines and more than half of human cancers have aberrantly upregulated phosphoinositide signals. How phospholipid signals are controlled during tumorigenesis is not fully understood (Fayngerts et al. 2014).
Literature References
PubMed ID Title Journal Year
21924498 The TIPE (TNFAIP8) family in inflammation, immunity, and cancer

Liu, S, Lou, Y

Mol. Immunol. 2011
25242044 TIPE3 is the transfer protein of lipid second messengers that promote cancer

Shi, Y, Liu, X, Fayngerts, SA, Chen, YH, Vourekas, A, Wang, Z, Liu, S, Sun, H, Oxley, CL, Cathopoulis, T, Zhang, L, Wu, J, Lemmon, MA, Cui, J

Cancer Cell 2014
25314070 A new TIPE of phosphoinositide regulator in cancer

Moniz, LS, Vanhaesebroeck, B

Cancer Cell 2014
25479791 Identical expression profiling of human and murine TIPE3 protein reveals links to its functions

Zhang, G, Shao, J, Zhang, W, Zhang, N, Liu, S, Hao, C, Cui, J

J. Histochem. Cytochem. 2015
Catalyst Activity

phosphatidylinositol transfer activity of TNFAIP8 proteins [cytosol]

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