A translationally regulated Tousled kinase phosphorylates histone H3 and confers radioresistance when overexpressed

Oncogene
Y LiA De Benedetti

Abstract

The gene Tousled of Arabidopsis Thaliana encodes a protein kinase which, when mutated, results in abnormal flower development. From a library of mRNAs that are translationally upregulated by overexpression of the translation initiation factor 4E, we identified a mammalian Tousled Like kinase (TLK1B). The human TLK1B mRNA contains a 5'UTR 1088-nt-long with two upstream AUG codons, and was found to be very inhibitory for translation. The TLK1B protein localizes almost exclusively to the nuclei. TLK1B overexpression in mammalian cells rendered them more resistant to ionizing radiation (IR). Purified TLK1B phosphorylated histone H3 at S(10) with high specificity both in a mix of core histones and in isolated chromatin, suggesting that histone H3 is a physiological substrate for TLK1B. Moreover, overexpression of TLK1B in transfected cells resulted in a higher degree of H3 phosphorylation. Expression of TLK1B in a yeast strain that harbors a temperature-sensitive mutation of the major H3 kinase, Ipl1, complemented the growth defect; restored normal levels of histone H3 phosphorylation; and increased their resistance to IR. Phosphorylation of H3 has been linked to the activation of the immediate-early genes upon mitogenic stimulation...Continue Reading

References

Apr 25, 1991·Nucleic Acids Research·A De Benedetti, R E Rhoads
Apr 1, 1994·Trends in Biochemical Sciences·A P Geballe, D R Morris
Apr 30, 1998·Current Opinion in Cell Biology·N Sonenberg, A C Gingras
Oct 6, 1998·Annual Review of Biochemistry·S Waga, B Stillman
Mar 13, 1999·Current Biology : CB·A CasamayorD R Alessi
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·A De Benedetti, A L Harris
Feb 2, 2000·The EMBO Journal·A E de la BarreS Dimitrov
May 16, 2000·The Journal of Biological Chemistry·V A PolunovskyP B Bitterman
Jul 6, 2000·Molecular Cell·S PyronnetN Sonenberg
Apr 1, 2001·Veterinary Anaesthesia and Analgesia·S A MoriyasuM P Moore

❮ Previous
Next ❯

Citations

Jun 14, 2005·Biochemical and Biophysical Research Communications·Reinhard KodymChristoph Fürweger
Jan 21, 2004·The Journal of Surgical Research·Kathryn S NortonBenjamin D L Li
Apr 1, 2008·Animal : an International Journal of Animal Bioscience·S OllierC Leroux
Mar 13, 2008·The Journal of Biological Chemistry·Gary M RieflerJill M Schumacher
Apr 26, 2013·Human Gene Therapy·Prakash Srinivasan Timiri ShanmugamGulshan Sunavala-Dossabhoy
May 1, 2002·Annals of Surgery·Benjamin D L LiArrigo DeBenedetti
Apr 25, 2006·Annals of Surgery·Kerry ByrnesBenjamin D Li
Aug 15, 2012·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Melissa D Lehti-Shiu, Shin-Han Shiu
Dec 22, 2009·BMC Molecular Biology·Caroline CanfieldArrigo De Benedetti
Sep 15, 2005·BMC Molecular Biology·Gulshan Sunavala-DossabhoyArrigo De Benedetti
Oct 24, 2006·BMC Molecular Biology·Siddhartha P Sen, Arrigo De Benedetti
Mar 7, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Ana M GarroteInés G Muñoz
Jan 1, 2012·ISRN Molecular Biology·Arrigo De Benedetti
Dec 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Constantine S MitsiadesKenneth C Anderson
Feb 19, 2013·Cell Host & Microbe·Patrick J DillonBlossom Damania
Feb 9, 2016·Free Radical Biology & Medicine·Prakash Srinivasan Timiri ShanmugamGulshan Sunavala-Dossabhoy
Feb 3, 2012·Journal of Comparative Pathology·T S Osborne, C Khanna
Jan 31, 2012·International Journal of Radiation Oncology, Biology, Physics·Gulshan Sunavala-DossabhoyGloria Caldito
Aug 14, 2010·Biochemical and Biophysical Research Communications·Chan-Hsien YehYi-Chun Wu
Aug 12, 2009·The Journal of Surgical Research·David J HillerBenjamin D L Li
Oct 23, 2008·DNA Repair·Gulshan Sunavala-Dossabhoy, Arrigo De Benedetti
Apr 1, 2008·Surgical Oncology Clinics of North America·Quyen D ChuBenjamin D Li
May 8, 2007·Journal of the American College of Surgeons·Kerry W ByrnesBenjamin D L Li
Jan 13, 2009·Journal of Experimental & Clinical Cancer Research : CR·Heather E KleinerBenjamin D L Li
Nov 15, 2003·Current Biology : CB·Zhenbo HanJill M Schumacher
Dec 5, 2003·Current Biology : CB·T Keith Blackwell, Amy K Walker
May 27, 2005·Current Biology : CB·Christopher T Richie, Andy Golden
Jan 1, 2016·AIMS Medical Science·Renjith Parameswaran Nair, Gulshan Sunavala-Dossabhoy
Jul 15, 2017·Cell Death and Differentiation·Sandra Segura-BayonaTravis H Stracker

❮ Previous
Next ❯

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.