Cellular processing pathways contribute to the activation of etoposide-induced DNA damage responses

DNA Repair
Jia-Rong FanTsai-Kun Li

Abstract

Cytotoxic action (tumor cell killing) and carcinogenic side effect (therapy-related secondary leukemia) of etoposide are closely related to its ability in stabilizing topoisomerase II cleavable complex (TOP2cc), a unique form of protein-linked DNA break. How cells process and detect TOP2-concealed DNA damage for the activation of downstream cellular responses remains unclear. Here, we showed proteasomal degradation of both TOP2 isozymes in a transcription-dependent manner upon etoposide treatment. Downregulation of TOP2 was preferentially associated with proteasomal removal of TOP2 in TOP2cc rather than proteolysis of free TOP2. Interestingly, blockage of TOP2 downregulation in TOP2cc also caused reduction in etoposide-induced activation of DNA damage molecules, an observation suggesting that the processing pathways of TOP2cc are involved in activation of etoposide-induced cellular responses. In this regard, we observed two TOP2cc processing pathways, replication- and transcription-initiated processing (RIP and TIP) with proteasome involved in the latter. Importantly, two processing pathways contributed to differential activation of various DNA damage signaling and downstream cellular responses. Etoposide-induced phosphorylatio...Continue Reading

References

Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·M T HowardK N Kreuzer
Jan 18, 1996·Nature·J M BergerJ C Wang
Jun 6, 1998·Biochimie·J Robert, A K Larsen
Sep 28, 1998·Biochimica Et Biophysica Acta·T Andoh, R Ishida
Sep 28, 1998·Biochimica Et Biophysica Acta·K R Hande
Sep 28, 1998·Biochimica Et Biophysica Acta·B C Baguley, L R Ferguson
Sep 28, 1998·Biochimica Et Biophysica Acta·C A Felix
Dec 30, 1999·Science·X YangJ C Wang
May 9, 2000·The Journal of Biological Chemistry·M E Shea, H Hiasa
Nov 30, 2000·The Journal of Biological Chemistry·R YeS P Lees-Miller
Jun 8, 2001·Molecular and Cellular Biology·H Zhao, H Piwnica-Worms
Sep 8, 2001·The Journal of Biological Chemistry·Y MaoL F Liu
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·James C Wang
May 29, 2003·Current Medicinal Chemistry. Anti-cancer Agents·Olivier SordetYves Pommier
Sep 25, 2003·Nature Reviews. Molecular Cell Biology·Michael R LieberKlaus Schwarz
Dec 23, 2003·The Journal of Biological Chemistry·Parima DarouiLeroy F Liu
Oct 9, 2004·The Journal of Biological Chemistry·Thelma ThompsonLyubomir T Vassilev
Feb 8, 2005·Biochemical and Biophysical Research Communications·Peilin ZhangFei Chen
Apr 15, 2005·The New England Journal of Medicine·Anita R MistryDavid Grimwade
Jul 5, 2006·Molecular Cancer Therapeutics·Mobeen MalikJohn L Nitiss
Jul 22, 2006·DNA Repair·Carolyn A FelixNeil Osheroff
Sep 16, 2006·The Journal of Biological Chemistry·Ailing ZhangLeroy F Liu
Jul 10, 2007·DNA Repair·Dorothee C Dartsch, Frank Gieseler

❮ Previous
Next ❯

Citations

Dec 31, 2009·Apoptosis : an International Journal on Programmed Cell Death·Ilona SchonnDorothee C Dartsch
Apr 21, 2009·Nature Reviews. Cancer·John L Nitiss
Oct 30, 2012·Nature Structural & Molecular Biology·Matthew J SchellenbergR Scott Williams
Aug 21, 2012·Antioxidants & Redox Signaling·V Ashutosh Rao
Nov 19, 2010·Cellular and Molecular Life Sciences : CMLS·Shang-Min ChouTsai-Kun Li
Jan 9, 2015·International Journal of Molecular Sciences·Ting ZhouVivienne I Rebel
Aug 20, 2015·Medicinal Research Reviews·Benny J EvisonSuzanne M Cutts
Jan 23, 2016·Biochemical Pharmacology·Ka C LeeCaroline A Austin
Jul 17, 2013·Journal of Cellular and Molecular Medicine·Hong-Quan DuongInsoo Bae
Aug 12, 2014·Environmental and Molecular Mutagenesis·Sara N AndresR Scott Williams
Jul 18, 2018·International Journal of Molecular Sciences·Ka Cheong LeeCaroline A Austin
Sep 14, 2019·Molecular Pharmacology·Ian G CowellCaroline A Austin
Jun 27, 2020·Molecular Pharmacology·Rebecca L SwanCaroline A Austin
Jun 10, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yng-Miin Toh, Tsai-Kun Li
Dec 6, 2012·Biology Open·Ka Cheong LeeCaroline A Austin
May 5, 2021·Molecular Pharmacology·Rebecca L SwanCaroline A Austin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.