Suppressor of fused regulates Gli activity through a dual binding mechanism

Molecular and Cellular Biology
Mark MerchantFrederic J de Sauvage

Abstract

The Hedgehog pathway drives proliferation and differentiation by activating the Gli/Ci family of zinc finger transcription factors. Gli/Ci proteins form Hedgehog signaling complexes with other signaling components, including the kinesin-like protein Costal-2, the serine-threonine kinase Fused, and Suppressor of Fused [Su(fu)]. In these complexes Gli/Ci proteins are regulated by cytoplasmic sequestration, phosphorylation, and proteolysis. Here we characterize structural and functional determinants of Su(fu) required for Gli regulation and show that Su(fu) contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1. While each domain is capable of binding to different Gli1 regions independently, interactions between Su(fu) and Gli1 at both sites are required for cytoplasmic tethering and repression of Gli1. Furthermore, we have solved the crystal structure of the amino-terminal domain of human Su(fu)(27-268) at 2.65 A resolution. This domain forms a concave pocket with a prominent acidic patch. Mutation at Asp(159) in the acidic patch disrupts Gli1 tethering and...Continue Reading

References

Sep 12, 1991·Nature·P W InghamY Nakano
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Nov 14, 1996·Nature·V MarigoC J Tabin
Feb 1, 1997·Journal of Molecular Endocrinology·S M LuohF J de Sauvage
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·P D AdamsA T Brünger
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·Y ChenS M Smolik
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·S W AuM J Adams
Oct 6, 1999·Current Opinion in Structural Biology·I Usón, G M Sheldrick
Nov 13, 1999·Nature Cell Biology·P KogermanP G Zaphiropoulos
May 12, 2000·Nature Cell Biology·M MuroneF J de Sauvage
May 29, 2000·The Journal of Biological Chemistry·M A StegmanD J Robbins
Jun 22, 2000·Journal of Molecular Biology·M Stewart, R P Baker
Aug 2, 2000·Mammalian Genome : Official Journal of the International Mammalian Genome Society·D Simon-ChazottesM F Blanchet-Tournier
Mar 17, 2001·Development Genes and Evolution·M DelattreM F Blanchet-Tournier
Apr 6, 2001·Gene·K A MarfatiaA H Corbett
Aug 18, 2001·The Journal of Biological Chemistry·R P BakerM Stewart
Dec 4, 2001·Genes & Development·P W Ingham, A P McMahon
Dec 6, 2001·Traffic·S M Steggerda, B M Paschal
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Steven Yan Cheng, J Michael Bishop
Jun 18, 2002·Nature Genetics·Michael D TaylorDavid Hogg

❮ Previous
Next ❯

Citations

Apr 22, 2009·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Vanessa MedinaJesús Espada
Jan 23, 2013·Cell Research·Yongbin Chen, Jin Jiang
Nov 10, 2013·Nature Medicine·Dereck AmakyeMarion Dorsch
Aug 16, 2006·Molecular and Cellular Biology·Alison R MeloniMarc G Caron
May 14, 2011·Cancer Research·Samer SinghDavid J Robbins
Aug 27, 2005·PLoS Genetics·Marco J KoudijsFredericus J M van Eeden
Jan 23, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Manuela Torres Andion VidalJean Nunes Dos Santos
May 6, 2015·Proceedings of the National Academy of Sciences of the United States of America·Yuhong HanJin Jiang
Jan 15, 2016·Cellular and Molecular Life Sciences : CMLS·Tatiana Gorojankina
Oct 27, 2015·Cellular and Molecular Life Sciences : CMLS·Annarita De LucaKetty Leto
Dec 22, 2006·Biochemical and Biophysical Research Communications·Kei TakenakaHiroaki Miki
Sep 11, 2014·Journal of Experimental & Clinical Cancer Research : CR·Chunyan ZengShiwen Luo
May 29, 2015·RNA Biology·Zhen XingLiuqing Yang
Jun 28, 2005·Cancer Letters·Leela Daya-Grosjean, Sophie Couvé-Privat
Dec 1, 2005·Differentiation; Research in Biological Diversity·Paul C BarnfieldChi-chung Hui
Aug 16, 2011·Developmental Biology·Tan H MinEdgar M Pera
Aug 2, 2007·Expert Opinion on Therapeutic Targets·Alex S KiselyovAlexandre V Ivachtchenko
May 10, 2007·Developmental Cell·Tamara CasparyKathryn V Anderson
Mar 24, 2010·Biochimica Et Biophysica Acta·Milena Saqui-Salces, Juanita L Merchant
Apr 18, 2009·Developmental Biology·Jinping JiaAimin Liu
Jan 18, 2006·Developmental Biology·Jennifer A CrokerRobert A Holmgren
Apr 6, 2006·Developmental Biology·Barbara E SissonRobert A Holmgren
Apr 18, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Laurence BrugièresJacques Grill
Feb 11, 2015·Expert Reviews in Molecular Medicine·Silvia Pandolfi, Barbara Stecca
Oct 30, 2015·Cancers·Sherri Y Huang, Jer-Yen Yang
Feb 4, 2016·Development·Raymond Teck Ho LeePhilip W Ingham
Sep 20, 2005·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jason K SicklickAnna Mae Diehl
Dec 13, 2005·Carcinogenesis·Jason K SicklickAnna Mae Diehl
Apr 17, 2019·Cells·Toshiki Terao, Yosuke Minami
May 29, 2016·The EMBO Journal·Madalina RaducuVincenzo D'Angiolella

❮ 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.