Wnt regulation: exploring Axin-Disheveled interactions and defining mechanisms by which the SCF E3 ubiquitin ligase is recruited to the destruction complex.

Molecular Biology of the Cell
Kristina SchaeferMark Peifer

Abstract

Wnt signaling plays key roles in embryonic development and adult stem cell homeostasis and is altered in human cancer. Signaling is turned on and off by regulating stability of the effector β-catenin (β-cat). The multiprotein destruction complex binds and phosphorylates β-cat and transfers it to the SCF-TrCP E3-ubiquitin ligase for ubiquitination and destruction. Wnt signals act though Dishevelled to turn down the destruction complex, stabilizing β-cat. Recent work clarified underlying mechanisms, but important questions remain. We explore β-cat transfer from the destruction complex to the E3 ligase, and test models suggesting Dishevelled and APC2 compete for association with Axin. We find that Slimb/TrCP is a dynamic component of the destruction complex biomolecular condensate, while other E3 proteins are not. Recruitment requires Axin and not APC, and Axin's RGS domain plays an important role. We find that elevating Dishevelled levels in Drosophila embryos has paradoxical effects, promoting the ability of limiting levels of Axin to turn off Wnt signaling. When we elevate Dishevelled levels, it forms its own cytoplasmic puncta, but these do not recruit Axin. Superresolution imaging in mammalian cells raises the possibility tha...Continue Reading

References

May 1, 1995·Genes & Development·S YanagawaR Nusse
Oct 1, 1996·Current Biology : CB·J Yang-SnyderR T Moon
Jun 7, 1997·Biochimica Et Biophysica Acta·P Polakis
Oct 6, 1997·The Journal of Biological Chemistry·K OrfordS W Byers
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·C LiuX He
Oct 12, 1999·Nature·J M PetersJ M Graff
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·C SakanakaL T Williams
May 16, 2000·The EMBO Journal·K E SpinkW I Weis
Oct 12, 2000·Biochemical and Biophysical Research Communications·M A JuliusJ Kitajewski
Jun 27, 2001·The Journal of Biological Chemistry·M KishidaA Kikuchi
Sep 27, 2002·Genesis : the Journal of Genetics and Development·Joseph B Duffy
Jan 7, 2004·Biochemical and Biophysical Research Communications·Jun LiuRaymond L White
Jan 21, 2004·Molecular Cell·Keiko TamaiXi He
May 19, 2007·Science·Michael B MajorRandall T Moon
May 29, 2007·Nature Structural & Molecular Biology·Thomas Schwarz-RomondMariann Bienz
Jul 4, 2007·Journal of Cell Science·Thomas Schwarz-RomondMariann Bienz
Sep 21, 2007·Journal of Cell Science·Wenqing Xu, David Kimelman
Jan 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Marc FiedlerMariann Bienz
Feb 3, 2011·The Journal of Biological Chemistry·Ondrej BernatikVitezslav Bryja
Oct 21, 2011·Journal of Proteome Research·Maximiliane Hilger, Matthias Mann
Mar 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Daniele V F TaurielloMadelon M Maurice
May 10, 2012·Cold Spring Harbor Perspectives in Biology·M Albert Basson

❮ Previous
Next ❯

Citations

Aug 22, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Qiaoni ShiYe-Guang Chen
Sep 15, 2021·Cancer Discovery·Marie J ParsonsLukas E Dow

❮ Previous
Next ❯

Datasets Mentioned

BETA
PXD016314

Methods Mentioned

BETA
transfect
affinity-purification
pull down
pull downs
co-IP
co-IPs
transfection
transfections
immunoprecipitation
acetylation

Software Mentioned

Photoshop
Fiji
Nikon
SIM
Fiji ImageJ
GraphPad
Slimb
MaxQuant

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.