The role of PACT in mediating gene induction, PKR activation, and apoptosis in response to diverse stimuli.

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Joao T MarquesGanes C Sen

Abstract

PACT, the protein activator of the double-stranded (ds)RNA-activated protein kinase (PKR) has been shown to strongly interact with and activate PKR in cultured cells and in vitro. To further analyze the functions of PACT we have recently generated PACT knockout (KO) mice and described several developmental defects that are absent in PKR KO mice. Importantly, PACT has been previously suggested to be involved in different signaling pathways that include endoplasmic reticulum stress, serum deprivation, growth factor withdrawal, viral infection, and cytokine responses. In this study, we have analyzed the contribution of PACT to these pathways using cells derived from wildtype (WT) and PACT KO mice. Notably, we have been unable to detect any significant differences in the responses to stress stimuli comparing WT and PACT KO cells, although we have been able to validate the specific interaction between PACT and PKR. Taken together, our results reinforce the importance of genetic loss of function analysis to infer protein function.

References

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Citations

Jan 30, 2015·Wiley Interdisciplinary Reviews. RNA·Alex HeyamMichael Plevin
Feb 14, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Juan A MarchalMaria A Garcia
Jan 3, 2021·The FEBS Journal·Evelyn ChukwurahMaria Hatzoglou
Mar 29, 2019·Frontiers in Immunology·Morgan E Brisse, Hinh Ly
Dec 1, 2009·Viruses·Bianca Dauber, Thorsten Wolff
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Aug 6, 2019·Frontiers in Immunology·Morgan Brisse, Hinh Ly
Aug 2, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pak-Yin LuiDong-Yan Jin
Dec 18, 2018·ACS Biomaterials Science & Engineering·Riley P AllenJamal S Lewis
Sep 1, 2021·Wiley Interdisciplinary Reviews. RNA·Alyssa M EnglishStephanie L Moon
Nov 15, 2008·Journal of Molecular Biology·Madhurima SinghRekha C Patel

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