A novel mouse Smad4 mutation reduces protein stability and wild-type protein levels

Mammalian Genome : Official Journal of the International Mammalian Genome Society
Yijing ChenTerry Magnuson

Abstract

Smad4 is a key signal transducer of the transforming growth factor-beta (TGF-beta) superfamily of growth factors that are critical regulators of embryonic patterning and adult tissue homeostasis. The biological activity of the TGF-beta signaling is tightly controlled at multiple levels, including the abundance of SMAD4 proteins. We previously recovered a novel allele of Smad4 in a gene-based screen in N-ethyl-N-nitrosourea (ENU)-mutagenized mouse embryonic stem cells. The mutation resulted in an unstable truncated protein that is degraded through proteasomal pathways. In the heterozygous state, this allele acts in a dominant negative fashion to reduce the wild-type protein level as well as signaling output. Biochemical characterization indicated that the truncated protein is able to form a complex with the wild-type protein, thus targeting it for proteasomal degradation as well. Phenotypic analyses of the heterozygous animals provided insight into the threshold requirement of Smad4-dependent signaling in vivo.

References

Apr 1, 1997·Current Biology : CB·Y ZhangR Derynck
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·X YangC Deng
Aug 26, 1998·Genes & Development·M Whitman
Oct 6, 1998·Annual Review of Biochemistry·J Massagué
Jun 8, 1999·Developmental Biology·L A Raftery, D J Sutherland
Feb 26, 2000·Molecular Biology of the Cell·K KusanagiK Miyazono
Mar 10, 2000·Cytokine & Growth Factor Reviews·J L Wrana, L Attisano
Mar 10, 2000·Cytokine & Growth Factor Reviews·M M Taketo, K Takaku
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·J Xu, L Attisano
Oct 6, 2000·The Journal of Biological Chemistry·L Jayaraman, J Massague
Sep 13, 2001·The Journal of Biological Chemistry·D MauriceC S Hill
Nov 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jay L VivianTerry Magnuson
Jun 10, 2003·The Journal of Biological Chemistry·Anita MorénAristidis Moustakas
Jan 1, 2006·CSH Protocols·Andras NagyRichard Behringer

❮ Previous
Next ❯

Citations

May 22, 2007·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Peter L OliverKay E Davies
Nov 7, 2012·Molecular and Cellular Biology·Ronald L ChandlerTerry Magnuson
Sep 2, 2011·The Journal of Clinical Investigation·Jennifer Nancy HahnFrank Robert Jirik
Nov 24, 2011·Endocrine-related Cancer·Sonia D'InzeoAnna Coppa
Apr 26, 2007·Nature Reviews. Immunology·Laurence C EisenlohrTania N Golovina
Oct 3, 2017·Surgical Neurology International·Nicholas T GamboaM Yashar S Kalani

❮ 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.