Intermolecular binding between TIFA-FHA and TIFA-pT mediates tumor necrosis factor alpha stimulation and NF-κB activation.

Molecular and Cellular Biology
Chia-Chi Flora HuangMing-Daw Tsai

Abstract

The forkhead-associated (FHA) domain recognizes phosphothreonine (pT) with high specificity and functional diversity. TIFA (TRAF-interacting protein with an FHA domain) is the smallest FHA-containing human protein. Its overexpression was previously suggested to provoke NF-κB activation, yet its exact roles in this signaling pathway and the underlying molecular mechanism remain unclear. Here we identify a novel threonine phosphorylation site on TIFA and show that this phosphorylated threonine (pT) binds with the FHA domain of TIFA, leading to TIFA oligomerization and TIFA-mediated NF-κB activation. Detailed analysis indicated that unphosphorylated TIFA exists as an intrinsic dimer and that the FHA-pT9 binding occurs between different dimers of TIFA. In addition, silencing of endogenous TIFA resulted in attenuation of tumor necrosis factor alpha (TNF-α)-mediated downstream signaling. We therefore propose that the TIFA FHA-pT9 binding provides a previously unidentified link between TNF-α stimulation and NF-κB activation. The intermolecular FHA-pT9 binding between dimers also represents a new mechanism for the FHA domain.

References

Mar 30, 2001·The Journal of Biological Chemistry·J M ZapataJ C Reed
Jan 19, 2002·Biochemical and Biophysical Research Communications·Mutsumi KanamoriYoshihide Hayashizaki
Mar 26, 2002·FEBS Letters·Daniel Durocher, Stephen P Jackson
May 25, 2002·Molecular and Cellular Biology·Xingzhi XuDavid F Stern
Sep 2, 2004·Molecular and Cellular Biology·M Lamar SeibenhenerMarie W Wooten
Oct 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chee-Kwee EaZhijian J Chen
Oct 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Roger A O'NeillPeter B Vander Horn
Jul 29, 2008·Accounts of Chemical Research·Xiangyang Liang, Steven R Van Doren
Dec 26, 2008·Science Signaling·Anjali MahajanMing-Daw Tsai
Sep 29, 2009·Molecular Cell·Zhenjian CaiNikola P Pavletich
Jun 1, 2010·Journal of Cellular Biochemistry·Kent Z Q WangPhilip E Auron
Jan 4, 2012·Biochemistry·Hsin-Hui WuMing-Daw Tsai
Jan 12, 2012·Nucleic Acids Research·Stephanie JungmichelStephen J Smerdon

❮ Previous
Next ❯

Citations

Sep 23, 2016·PLoS Pathogens·Ryan G Gaudet, Scott D Gray-Owen
Dec 15, 2016·Proceedings of the National Academy of Sciences of the United States of America·Ting-Yang LinJohn Y-J Shyy
Nov 1, 2018·Chembiochem : a European Journal of Chemical Biology·Wei-Cheng HuangMing-Daw Tsai
Nov 21, 2018·EMBO Reports·Diego García-WeberCécile Arrieumerlou
Jul 15, 2020·Annual Review of Microbiology·Katherine Andrea SchubertVictoria Auerbuch
Jul 28, 2019·Life Science Alliance·Kornelia EllwangerThomas A Kufer
May 27, 2020·Chembiochem : a European Journal of Chemical Biology·Lina LiangStéphane P Vincent
Mar 22, 2020·Scientific Reports·Teruya NakamuraYuriko Yamagata
Jun 28, 2020·Cellular and Molecular Life Sciences : CMLS·Diego García-Weber, Cécile Arrieumerlou
Jul 22, 2016·Signal Transduction and Targeted Therapy·Wenzhi ShenRong Xiang
Oct 6, 2018·Acta Crystallographica. Section D, Structural Biology·Changlin XieFudong Li
Feb 27, 2020·Cell Reports·Madeline NiederkornDaniel T Starczynowski
May 15, 2021·Organic & Biomolecular Chemistry·Lina LiangStéphane P Vincent
Jul 10, 2021·Scientific Reports·Hao-Chih ChangShih-Hsien Sung

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aphasia

Aphasia affects the ability to process language, including formulation and comprehension of language and speech, as well as the ability to read or write. Here is the latest research on aphasia.