A variant of nuclear localization signal of bipartite-type is required for the nuclear translocation of hypoxia inducible factors (1alpha, 2alpha and 3alpha)

Oncogene
J C Luo, M Shibuya

Abstract

Hypoxia inducible factors (HIF1, 2 and 3), consisting of alpha and beta subunits, play an essential role in various responses to hypoxia. Nuclear entry of alpha subunits is a necessary step for the formation of DNA-binding complex with beta subunit, which is constitutively localized in the nucleus. We show here that the nuclear accumulation of HIF2alpha induced by hypoxia is mediated through a novel variant of bipartite-type nuclear localization signal (NLS) in the C-terminus of the protein, which has an unusual length of spacer sequence between two adjacent basic domains. We further show that when the ubiquitin-proteasome system was deficient or inhibited, HIF2alpha accumulated in the nucleus even under normoxia, also mediated through the bipartite NLS. These findings indicate that the protein stability is critical for the nuclear localization of HIF2alpha and hypoxia is not a necessary factor for the process. Importantly, the NLS of HIF2alpha is also conserved in the other HIF family members, HIF1alpha and HIF3alpha. Mutational analyses proved that the NLS mediating the nuclear localization of HIF1alpha is indeed bipartite-, but not monopartite-type as thought before. Our results suggest that the newly identified NLS is cruci...Continue Reading

References

May 25, 1991·Nucleic Acids Research·Y ImaiM Terada
Dec 1, 1991·Trends in Biochemical Sciences·C Dingwall, R A Laskey
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
Aug 27, 1993·Cell·R A Laskey, C Dingwall
Jul 1, 1996·Physiological Reviews·D A Jans, S Hübner
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·O IliopoulosM A Goldberg
Feb 28, 1998·The Journal of Biological Chemistry·T IkutaK Kawajiri
May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·J B HogeneschC A Bradfield
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·L E HuangH F Bunn
Oct 31, 1998·Current Opinion in Genetics & Development·G L Semenza
Nov 20, 1998·Trends in Genetics : TIG·W G Kaelin, E R Maher
Nov 24, 1999·The Journal of Biological Chemistry·P W ConradD E Millhorn
May 24, 2000·The Journal of Biological Chemistry·M E CockmanP H Maxwell

❮ Previous
Next ❯

Citations

Mar 30, 2004·Biochemical and Biophysical Research Communications·Ryo TakahashiShuntaro Hara
Jun 6, 2002·European Journal of Biochemistry·Maria G Romanelli, Carlo Morandi
Mar 12, 2008·Molecular and Cellular Biology·Nuria M RomeroPablo Wappner
Sep 7, 2002·Molecular and Cellular Biology·Sofía Lavista-LlanosPablo Wappner
Sep 16, 2003·Molecular and Cellular Biology·Shuhei TomitaYousuke Takahama
Jul 17, 2004·American Journal of Respiratory Cell and Molecular Biology·Georgia ChachamiEfrosyni Paraskeva
May 10, 2001·Cell Structure and Function·M Shibuya
Feb 27, 2009·Future Oncology·Mireille Khacho, Stephen Lee
Jun 17, 2006·FEBS Letters·Sonja HägeleDörthe M Katschinski
May 9, 2015·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Luke Gammon, Ian C Mackenzie
Oct 1, 2009·Biochemical and Biophysical Research Communications·Georgia ChachamiGeorge Simos
Jun 23, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·José G Soñanez-OrganisGloria Yepiz-Plascencia
Feb 24, 2007·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Tiandao Li, Marius Brouwer
May 10, 2005·Experimental Cell Research·Maria Hägg, Stefan Wennström
Jan 12, 2008·Biochimica Et Biophysica Acta·Reinhard DeppingMatthias Köhler
Aug 26, 2016·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Omar KujanCamile S Farah
Jul 6, 2004·Oncogene·Junko Kawamura-TsuzukuTadashi Yamamoto
Jul 4, 2018·Journal of Cellular Physiology·Christina Befani, Panagiotis Liakos
Mar 1, 2018·Oncogene·Amina M Abdul-AzizStuart A Rushworth
Jan 24, 2019·Current Oncology Reports·Jaleh Fallah, Brian I Rini
Mar 27, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Reinhard DeppingFriederike Katharina Kosyna
Jul 6, 2019·Molecular Biology and Evolution·Xuexue LiuLin Jiang
Nov 1, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shan GaoCunming Duan
May 20, 2003·The Journal of Biological Chemistry·Astrid A A M Danen-Van OorschotMathieu H M Noteborn
Jun 7, 2003·The Journal of Biological Chemistry·Larbi AmazitAnne Guiochon-Mantel
Apr 10, 2019·Journal of Cell Science·Ioanna-Maria GkotinakouPanagiotis Liakos
Sep 27, 2019·International Journal of Molecular Sciences·Beata Greb-Markiewicz, Marta Kolonko
Mar 6, 2019·Cells·Ilias MylonisEfrosyni Paraskeva

❮ 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.