FANCJ protein is important for the stability of FANCD2/FANCI proteins and protects them from proteasome and caspase-3 dependent degradation

Oncotarget
David W ClarkKomaraiah Palle

Abstract

Fanconi anemia (FA) is a rare genome instability syndrome with progressive bone marrow failure and cancer susceptibility. FANCJ is one of 17 genes mutated in FA-patients, comprises a DNA helicase that is vital for properly maintaining genomic stability and is known to function in the FA-BRCA DNA repair pathway. While exact role(s) of FANCJ in this repair process is yet to be determined, it is known to interact with primary effector FANCD2. However, FANCJ is not required for FANCD2 activation but is important for its ability to fully respond to DNA damage. In this report, we determined that transient depletion of FANCJ adversely affects stability of FANCD2 and its co-regulator FANCI in multiple cell lines. Loss of FANCJ does not significantly alter cell cycle progression or FANCD2 transcription. However, in the absence of FANCJ, the majority of FANCD2 is degraded by both the proteasome and Caspase-3 dependent mechanism. FANCJ is capable of complexing with and stabilizing FANCD2 even in the absence of a functional helicase domain. Furthermore, our data demonstrate that FANCJ is important for FANCD2 stability and proper activation of DNA damage responses to replication blocks induced by hydroxyurea.

References

Oct 23, 1997·American Journal of Human Genetics·H JoenjeF Arwert
Mar 10, 2001·Molecular Cell·I Garcia-HigueraA D D'Andrea
Oct 24, 2002·Blood·Philip S RosenbergBlanche P Alter
Sep 16, 2003·Nature Genetics·Amom Ruhikanta MeeteiWeidong Wang
Nov 25, 2003·Blood·Marieke LevitusHans Joenje
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sharon CantorDavid M Livingston
Jun 17, 2004·Molecular and Cellular Biology·XiaoZhe WangAlan D D'Andrea
May 10, 2005·The Journal of Biological Chemistry·Rigu GuptaRobert M Brosh
Aug 24, 2005·Nature Genetics·Marieke LevitusHans Joenje
Dec 17, 2005·Cell Cycle·Sharon B Cantor, Paul R Andreassen
Aug 1, 2007·Molecular and Cellular Biology·Easwari Kumaraswamy, Ramin Shiekhattar
Nov 4, 2008·The Journal of Biological Chemistry·Timothy B C LondonKevin Hiom
Dec 23, 2008·Mutation Research·Meghan A RegoNiall G Howlett
Jan 20, 2009·The Journal of Biological Chemistry·Joshua A SommersRobert M Brosh
Aug 3, 2010·Chromosoma·Fan ZhangPaul R Andreassen
Aug 18, 2010·Genes & Development·Younghoon Kee, Alan D D'Andrea
Feb 18, 2011·Genes & Development·Amitabh V NimonkarStephen C Kowalczykowski
Apr 12, 2011·International Journal of Hematology·Minoru Takata
Oct 26, 2011·Trends in Genetics : TIG·Avvaru N Suhasini, Robert M Brosh
Jul 4, 2012·Nucleic Acids Research·Archana SareenAlexandra Sobeck
Jul 14, 2012·PLoS Genetics·Jenny XieSharon B Cantor
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Mar 27, 2013·Molecular and Cellular Biology·Avvaru N SuhasiniRobert M Brosh
Mar 27, 2013·The Journal of Cell Biology·Rebekka A SchwabWojciech Niedzwiedz
Jul 30, 2014·The Journal of Biological Chemistry·Xiaoyong ChenGary M Kupfer
Sep 2, 2014·FEBS Letters·Wataru Sakai, Kaoru Sugasawa
Dec 5, 2014·Cancer Discovery·Sarah L SawyerRoger A Greenberg
Apr 14, 2015·Molecular Cell·Xinjian LiuChuan-Yuan Li

❮ Previous
Next ❯

Citations

Apr 21, 2016·Cell Cycle·Xiaoshan ZhangRandy J Legerski
Apr 7, 2017·Journal of breast cancer·Ananthapur VenkateshwariKomaraiah Palle
Apr 16, 2016·Oncotarget·Jayabal PanneerselvamPeiwen Fei
Aug 12, 2021·Neoplasia : an International Journal for Oncology Research·Chinnadurai ManiKomaraiah Palle
Aug 30, 2021·Molecular Cancer·Salvatore BenfattoBalca R Mardin

❮ Previous
Next ❯

Datasets Mentioned

BETA
AB16048

Methods Mentioned

BETA
transfection
FACS
co-immunoprecipitation
pull down

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.