Cytoplasmic TRAF4 contributes to the activation of p70s6k signaling pathway in breast cancer

Oncotarget
Hua-Yan RenXiaoyi Mi

Abstract

Tumor necrosis factor receptor associated factor 4 (TRAF4) is an important adaptor protein that plays a significant role in several signaling pathways. By studying the relationship between TRAF4 and 70 kDa ribosomal protein S6 kinase (p70s6k) in vivo, we demonstrated that cytoplasmic TRAF4 was correlated with the activation of p70s6k in breast cancer. Moreover, we found that cytoplasmic TRAF4 expression in breast cancer patients was significantly associated with a poor prognosis. To determine the exact mechanism, we analyzed the interaction between TRAF4 and p70s6k and identified the Zinc fingers domain of TRAF4 was responsible for their interaction in MCF7 cells. Furthermore, we found that activation of p70s6k/S6 signaling pathway by TRAF4 requires the mammalian target of rapamycin (mTOR) activity; TRAF4 acted as a sensitizer. Tumor necrosis factor receptor associated factor 2 (TRAF2), as a binding partner of TRAF4, could also promoted activation of p70s6k signaling via upregulating cytoplasm expression of TRAF4 and played a critical role in TNFa-induced activation of p70s6k/S6 pathway. Finally, we demonstrated p70s6k/S6 signaling pathway played an important role in the promoting function of TRAF4 on cell proliferation. In sum...Continue Reading

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Citations

May 12, 2018·International Journal of Oncology·Qiang KangXiao-Wen Zhang
Sep 26, 2019·American Journal of Physiology. Cell Physiology·Archita DasTohru Fukai
May 2, 2018·The Journal of Clinical Investigation·Ramesh SinghPing Yi
Oct 9, 2018·Frontiers in Immunology·Sining ZhuPing Xie
Nov 24, 2020·Frontiers in Cell and Developmental Biology·Wei ZhouQifa Ye

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Methods Mentioned

BETA
co-immunoprecipitation
transfection

Related Concepts