Stat3 cleavage by caspases: impact on full-length Stat3 expression, fragment formation, and transcriptional activity

The Journal of Biological Chemistry
James W DarnowskiY Eugene Chin

Abstract

Stat3 and its isoforms belong to a family of cytoplasmic transcription factors that affect the synthesis of various proteins. Caspases are cysteinyl-aspartate proteases that function under apoptotic and non-apoptotic conditions. We now report that, in addition to transcriptional splicing, Stat3 fragmentation can be mediated by caspases. Caspase activation in DU145 cells was achieved by staurosporine (STS) exposure, and Western analysis revealed a reduction in full-length Stat3 (fl-Stat3) expression that was caspase-mediated. This proteolytic relationship was further studied by exposing purified Stat3 protein to a mixture of active caspases under cell-free conditions. This demonstrated that caspases directly cleaved Stat3 and Stat3 cleavage was accompanied by the apparent formation of cleavage fragment(s). Stat3 cleavage fragments, reflecting multiple caspase cleavage sites, also were observed in vitro following STS exposure in DU145 cells and in HEK293T cells transfected to express Stat3 truncation mutants. The impact of cleavage on Stat3 transcriptional activity next was assessed and revealed that cleavage of fl-Stat3 was accompanied by reductions in Stat3-DNA binding, Stat3-driven reporter protein (luciferase) activity, and t...Continue Reading

References

Jan 1, 1991·Journal of Neurochemistry·N YanagiharaE Miyamoto
Jan 16, 1989·Biochemical and Biophysical Research Communications·H Matsumoto, Y Sasaki
Mar 13, 1986·Biochemical and Biophysical Research Communications·T TamaokiF Tomita
Oct 6, 1995·The Journal of Biological Chemistry·A G RosmarinC P Simkevich
Feb 1, 1995·Trends in Genetics : TIG·J N Ihle, I M Kerr
Nov 1, 1996·Molecular and Cellular Biology·D WangJ N Ihle
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·L H Boise, C B Thompson
May 23, 1997·The Journal of Biological Chemistry·C MiossecA Diu-Hercend
Sep 12, 1997·Science·J E Darnell
Feb 14, 1998·The Journal of Cell Biology·Y IshizakiM C Raff
May 16, 1998·The Journal of Biological Chemistry·P King, S Goodbourn
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·B B ZhouM W Kirschner
Aug 28, 1998·Science·A Ashkenazi, V M Dixit
Jan 23, 1999·Cell Death and Differentiation·C Stroh, K Schulze-Osthoff
Feb 2, 1999·The Journal of Experimental Medicine·P MarrackT Mitchell
Mar 10, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R Starr, D J Hilton
Mar 11, 1999·Journal of Receptor and Signal Transduction Research·M H Heim
Mar 20, 1999·The Journal of Biological Chemistry·H R StennickeG S Salvesen
Apr 21, 1999·Current Opinion in Cell Biology·A Ashkenazi, V M Dixit
Jun 22, 1999·Molecular and Cellular Biology·E YangJ E Darnell
Aug 24, 1999·Cell·J F BrombergJ E Darnell
Jun 13, 2000·Oncogene·T BowmanR Jove
Mar 10, 2001·Cold Spring Harbor Symposia on Quantitative Biology·J M AdamsS Cory
Feb 2, 2002·Science·Ali H Brivanlou, James E Darnell
Feb 19, 2002·Oncogene·Lena ThyrellDan Grandér
Mar 26, 2003·Genes & Development·Leonardo SalmenaRazqallah Hakem
Jun 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·N Eric OlsonEdward A Clark

❮ Previous
Next ❯

Citations

Jan 15, 2011·Cell Death and Differentiation·E A AfanasyevaF Westermann
Jan 12, 2007·Molecular BioSystems·Cheh Peng Lim, Xinmin Cao
Sep 3, 2009·Annals of the New York Academy of Sciences·Bharat B AggarwalBokyung Sung
Oct 23, 2014·Tropical Animal Health and Production·Tingxian DengXianwei Liang
Mar 2, 2012·The Journal of Biological Chemistry·Olga A TimofeevaAnatoly Dritschilo
Aug 31, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Zhimin HuYu Li
Jun 24, 2020·Journal of Food Biochemistry·Yun-Fei GeLong-Kui Cao
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chie WatanabeEdward A Clark
May 9, 2014·Oncotarget·Verena LichtThorsten Heinzel
Mar 14, 2020·Genetics and Molecular Biology·Sundas ArshadFazeeha Amjad
May 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Devasis ChatterjeeMurray B Resnick
Mar 7, 2015·Cancer Research·Shuangshuang ZhongJiong Deng
Feb 26, 2021·Breast Cancer Research and Treatment·Yi-Fei WangYi Ding

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.