HDACs class II-selective inhibition alters nuclear receptor-dependent differentiation

Journal of Molecular Endocrinology
Angela NebbiosoLucia Altucci

Abstract

Epigenetic deregulation contributes to diseases including cancer, neurodegeneration, osteodystrophy, cardiovascular defects, and obesity. For this reason, several inhibitors for histone deacetylases (HDACs) are being validated as novel anti-cancer drugs in clinical studies and display important anti-proliferative activities. While most inhibitors act on both class I, II, and IV HDACs, evidence is accumulating that class I is directly involved in regulation of cell growth and death, whereas class II members regulate differentiation processes, such as muscle and neuronal differentiation. Here, we show that the novel class II-selective inhibitor MC1568 interferes with the RAR- and peroxisome proliferator-activated receptor γ (PPARγ)-mediated differentiation-inducing signaling pathways. In F9 cells, this inhibitor specifically blocks endodermal differentiation despite not affecting retinoic acid-induced maturation of promyelocytic NB4 cells. In 3T3-L1 cells, MC1568 attenuates PPARγ-induced adipogenesis, while the class I-selective MS275 blocked adipogenesis completely thus revealing a different mode of action and/or target profile of the two classes of HDACs. Using in vivo reporting PPRE-Luc mice, we find that MC1568 impairs PPARγ ...Continue Reading

Citations

Jun 18, 2011·The Journal of Biological Chemistry·Tapan K ChatterjeeNeal L Weintraub
May 9, 2014·European Journal of Cell Biology·Yuanfei ZhouSiwen Jiang
Apr 11, 2015·International Journal of Molecular Sciences·Adriana BasilePaola Bontempo
Oct 16, 2012·Trends in Endocrinology and Metabolism : TEM·Maria M Mihaylova, Reuben J Shaw
Apr 23, 2016·Neurochemistry International·Haifa KassisZheng Gang Zhang
Jan 15, 2013·Biochemical and Biophysical Research Communications·Kumi MorikawaYasuaki Shirayoshi
Sep 6, 2014·Cellular and Molecular Life Sciences : CMLS·Eros Di GiorgioClaudio Brancolini
Jan 23, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Basak IcliMark W Feinberg
Sep 29, 2011·Nature Reviews. Molecular Cell Biology·Ana G Cristancho, Mitchell A Lazar
May 2, 2015·Brain Tumor Pathology·Mario VenzaIsabella Venza
Mar 5, 2019·Current Topics in Medicinal Chemistry·Xiaopeng PengJianjun Chen
May 21, 2019·Oncotarget·Kiran MadugulaPooja Jain
May 24, 2012·Current Opinion in Clinical Nutrition and Metabolic Care·Melina M Musri, Marcelina Párrizas
Apr 5, 2017·Stem Cells International·Gregory M Kelly, Mohamed I Gatie
Jun 10, 2017·International Journal of Molecular Sciences·Hirotaka Yoshioka, Yuji Yoshiko
Jul 24, 2020·Molecular Medicine·Xian ShiGuo-Jun Zhao
Dec 4, 2014·The Journal of Pharmacology and Experimental Therapeutics·Luigi FormisanoLorella M T Canzoniero
Jun 25, 2014·Cancer Research·Yun-Han LeeSnorri S Thorgeirsson
Feb 28, 2013·Development·Hendrikus J van HeesbeenMarten P Smidt

❮ 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.

Related Papers

The Journal of Biological Chemistry
Tapan K ChatterjeeNeal L Weintraub
The Journal of Biological Chemistry
Diane C Lagace, Mark W Nachtigal
The Journal of Biological Chemistry
Michael HaberlandEric N Olson
Cell Differentiation and Development : the Official Journal of the International Society of Developmental Biologists
C L MummeryS Shen
© 2021 Meta ULC. All rights reserved