scholarly journals Histone Variant H3.3 Mutations in Defining the Chromatin Function in Mammals

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2716
Author(s):  
Matteo Trovato ◽  
Vibha Patil ◽  
Maja Gehre ◽  
Kyung Min Noh

The systematic mutation of histone 3 (H3) genes in model organisms has proven to be a valuable tool to distinguish the functional role of histone residues. No system exists in mammalian cells to directly manipulate canonical histone H3 due to a large number of clustered and multi-loci histone genes. Over the years, oncogenic histone mutations in a subset of H3 have been identified in humans, and have advanced our understanding of the function of histone residues in health and disease. The oncogenic mutations are often found in one allele of the histone variant H3.3 genes, but they prompt severe changes in the epigenetic landscape of cells, and contribute to cancer development. Therefore, mutation approaches using H3.3 genes could be relevant to the determination of the functional role of histone residues in mammalian development without the replacement of canonical H3 genes. In this review, we describe the key findings from the H3 mutation studies in model organisms wherein the genetic replacement of canonical H3 is possible. We then turn our attention to H3.3 mutations in human cancers, and discuss H3.3 substitutions in the N-terminus, which were generated in order to explore the specific residue or associated post-translational modification.

Author(s):  
Abhishek Mohanty ◽  
Rodolfo Zunino ◽  
Vincent Soubannier ◽  
Shilpa Dilipkumar

2019 ◽  
Vol 81 (1) ◽  
pp. 453-482 ◽  
Author(s):  
Diane M. Ward ◽  
Suzanne M. Cloonan

Mitochondria are an iconic distinguishing feature of eukaryotic cells. Mitochondria encompass an active organellar network that fuses, divides, and directs a myriad of vital biological functions, including energy metabolism, cell death regulation, and innate immune signaling in different tissues. Another crucial and often underappreciated function of these dynamic organelles is their central role in the metabolism of the most abundant and biologically versatile transition metals in mammalian cells, iron. In recent years, cellular and animal models of mitochondrial iron dysfunction have provided vital information in identifying new proteins that have elucidated the pathways involved in mitochondrial homeostasis and iron metabolism. Specific signatures of mitochondrial iron dysregulation that are associated with disease pathogenesis and/or progression are becoming increasingly important. Understanding the molecular mechanisms regulating mitochondrial iron pathways will help better define the role of this important metal in mitochondrial function and in human health and disease.


2007 ◽  
Vol 35 (6) ◽  
pp. 1473-1478 ◽  
Author(s):  
M. Fukata ◽  
M.T. Abreu

The colonic epithelium is lined along its apical membrane with ∼1014 bacteria/g of tissue. Commensal bacteria outnumber mammalian cells in the gut severalfold. The reason for this degree of commensalism probably resides in the recent recognition of the microbiome as an important source of metabolic energy in the setting of poorly digestible nutrients. As in many themes in biology, the host may have sacrificed short-term benefit, i.e. nutritional advantages, for long-term consequences, such as chronic inflammation or colon cancer. In the present review, we examine the role of TLR (Toll-like receptor) signalling in the healthy host and the diseased host. We pay particular attention to the role of TLR signalling in idiopathic IBD (inflammatory bowel disease) and colitis-associated carcinogenesis. In general, TLR signalling in health contributes to homoeostatic functions. These include induction of antimicrobial peptides, proliferation and wound healing in the intestine. The pathogenesis of IBD, ulcerative colitis and Crohn's disease may be due to increased TLR or decreased TLR signalling respectively. Finally, we discuss the possible role of TLR signalling in colitis-associated neoplasia.


2013 ◽  
Vol 55 ◽  
pp. 133-151 ◽  
Author(s):  
G. Vignir Helgason ◽  
Tessa L. Holyoake ◽  
Kevin M. Ryan

Autophagy is a process that takes place in all mammalian cells and ensures homoeostasis and quality control. The term autophagy [self (auto)-eating (phagy)] was first introduced in 1963 by Christian de Duve, who discovered the involvement of lysosomes in the autophagy process. Since then, substantial progress has been made in understanding the molecular mechanism and signalling regulation of autophagy and several reviews have been published that comprehensively summarize these findings. The role of autophagy in cancer has received a lot of attention in the last few years and autophagy modulators are now being tested in several clinical trials. In the present chapter we aim to give a brief overview of recent findings regarding the mechanism and key regulators of autophagy and discuss the important physiological role of mammalian autophagy in health and disease. Particular focus is given to the role of autophagy in cancer prevention, development and in response to anticancer therapy. In this regard, we also give an updated list and discuss current clinical trials that aim to modulate autophagy, alone or in combination with radio-, chemo- or targeted therapy, for enhanced anticancer intervention.


1999 ◽  
Vol 274 (18) ◽  
pp. 12252-12256 ◽  
Author(s):  
Alex G. Therien ◽  
Steven J. D. Karlish ◽  
Rhoda Blostein

2021 ◽  
Vol 7 (10) ◽  
pp. 875
Author(s):  
Manuela Gómez-Gaviria ◽  
Ana P. Vargas-Macías ◽  
Laura C. García-Carnero ◽  
Iván Martínez-Duncker ◽  
Héctor M. Mora-Montes

Protein glycosylation is a highly conserved post-translational modification among organisms. It plays fundamental roles in many biological processes, ranging from protein trafficking and cell adhesion to host–pathogen interactions. According to the amino acid side chain atoms to which glycans are linked, protein glycosylation can be divided into two major categories: N-glycosylation and O-glycosylation. However, there are other types of modifications such as the addition of GPI to the C-terminal end of the protein. Besides the importance of glycoproteins in biological functions, they are a major component of the fungal cell wall and plasma membrane and contribute to pathogenicity, virulence, and recognition by the host immunity. Given that this structure is absent in host mammalian cells, it stands as an attractive target for developing selective compounds for the treatment of fungal infections. This review focuses on describing the relationship between protein glycosylation and the host–immune interaction in medically relevant fungal species.


Fermentation ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. 41 ◽  
Author(s):  
Vasiliki Lolou ◽  
Mihalis I. Panayiotidis

Scientific and commercial interest of probiotics, prebiotics and their effect on human health and disease has increased in the last decade. The aim of this review article is to evaluate the role of pro- and prebiotics on the normal function of healthy skin as well as their role in the prevention and therapy of skin disease. Lactobacilli and Bifidobacterium are the most commonly used probiotics and thought to mediate skin inflammation, treat atopic dermatitis (AD) and prevent allergic contact dermatitis (ACD). Probiotics are shown to decolonise skin pathogens (e.g., P. aeruginosa, S. aureus, A. Vulgaris, etc.) while kefir is also shown to support the immunity of the skin and treat skin pathogens through the production of antimicrobial substances and prebiotics. Finally, prebiotics (e.g., Fructo-oligosaccharides, galacto-oligosaccharides and konjac glucomannan hydrolysates) can contribute to the treatment of diseases including ACD, acne and photo aging primarily by enhancing the growth of probiotics.


2020 ◽  
Vol 21 (1) ◽  
pp. 52-65
Author(s):  
Sridhar Muthusami ◽  
Balasubramanian Vidya ◽  
Esaki M Shankar ◽  
Jamuna Vadivelu ◽  
Ilangovan Ramachandran ◽  
...  

Hormones are known to influence various body systems that include skeletal, cardiac, digestive, excretory, and immune systems. Emerging investigations suggest the key role played by secretions of endocrine glands in immune cell differentiation, proliferation, activation, and memory attributes of the immune system. The link between steroid hormones such as glucocorticoids and inflammation is widely known. However, the role of peptide hormones and amino acid derivatives such as growth and thyroid hormones, prolactin, dopamine, and thymopoietin in regulating the functioning of the immune system remains unclear. Here, we reviewed the findings pertinent to the functional role of hormone-immune interactions in health and disease and proposed perspective directions for translational research in the field.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joseph M. McEwen ◽  
Sasha Fraser ◽  
Alexxandra L. Sosa Guir ◽  
Jaydev Dave ◽  
Rebecca A. Scheck

AbstractThe methylglyoxal-derived hydroimidazolone isomer, MGH-1, is an abundant advanced glycation end-product (AGE) associated with disease and age-related disorders. As AGE formation occurs spontaneously and without an enzyme, it remains unknown why certain sites on distinct proteins become modified with specific AGEs. Here, we use a combinatorial peptide library to determine the chemical features that favor MGH-1. When properly positioned, tyrosine is found to play an active mechanistic role that facilitates MGH-1 formation. This work offers mechanistic insight connecting multiple AGEs, including MGH-1 and carboxyethylarginine (CEA), and reconciles the role of negative charge in influencing glycation outcomes. Further, this study provides clear evidence that glycation outcomes can be influenced through long- or medium-range cooperative interactions. This work demonstrates that these chemical features also predictably template selective glycation on full-length protein targets expressed in mammalian cells. This information is vital for developing methods that control glycation in living cells and will enable the study of glycation as a functional post-translational modification.


Sign in / Sign up

Export Citation Format

Share Document