Skp2 inhibits osteogenesis by promoting ubiquitin-proteasome degradation of Runx2

Biochimica Et Biophysica Acta
Gatha ThackerArun Kumar Trivedi

Abstract

Osteogenic transcription factor Runx2 is essential for osteoblast differentiation. The activity of Runx2 is tightly regulated at transcriptional as well as post-translational level. However, regulation of Runx2 stability by ubiquitin mediated proteasomal degradation by E3 ubiquitin ligases is little-known. Here, for the first time we demonstrate that Skp2, an SCF family E3 ubiquitin ligase negatively targets Runx2 by promoting its polyubiquitination and proteasome dependent degradation. Co-immunoprecipitation studies revealed that Skp2 physically interacts with Runx2 both in a heterologous as well as physiologically relevant system. Functional consequences of Runx2-Skp2 physical interaction were then assessed by promoter reporter assay. We show that Skp2-mediated downregulation of Runx2 led to reduced Runx2 transactivation and osteoblast differentiation. On the contrary, inhibition of Skp2 restored Runx2 levels and promoted osteoblast differentiation. We further show that Skp2 and Runx2 proteins are co-expressed and show inverse relation in vivo such as in lactating, ovariectomized and estrogen-treated ovariectomized animals. Together, these data demonstrate that Skp2 targets Runx2 for ubiquitin mediated degradation and hence n...Continue Reading

References

Aug 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y W ZhangY Ito
Dec 6, 2000·Seminars in Cell & Developmental Biology·G Karsenty
Dec 7, 2000·The Journal of Biological Chemistry·B KernG Karsenty
Oct 3, 2002·Journal of Cell Science·Kimberly S HarringtonGary S Stein
Aug 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Takumi KamuraKeiichi I Nakayama
Jan 1, 2004·The Journal of Biological Chemistry·Ming ZhaoDi Chen
Jan 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Haojie HuangDonald J Tindall
Sep 28, 2005·Birth Defects Research. Part C, Embryo Today : Reviews·Tania M SchroederJennifer J Westendorf
Apr 15, 2006·The Journal of Biological Chemistry·Run ShenDi Chen
May 27, 2006·Science·Dallas C JonesLaurie H Glimcher
Sep 6, 2007·PloS One·Fumitaka KugimiyaUng-il Chung
May 27, 2008·Nature Reviews. Cancer·David Frescas, Michele Pagano
Jun 11, 2008·The Journal of Cell Biology·Xueni LiZhijie Chang
Sep 8, 2009·Journal of Dental Research·J H JonasonD Chen
Aug 27, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Eun-Jung AnnHee-Sae Park
Jan 17, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Yi-Feng HuangShih-Chieh Hung
Jul 4, 2013·Biochimica Et Biophysica Acta·Savita LochabArun Kumar Trivedi
Nov 7, 2015·The Journal of Biological Chemistry·Yogesh KumarArun Kumar Trivedi

❮ Previous
Next ❯

Citations

Nov 15, 2020·Molecular Cancer Research : MCR·Mukul MishraArun Kumar Trivedi
Apr 4, 2021·The Journal of Biological Chemistry·Yizhen HuangJianjun Ma

❮ 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.