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Progress in Molecular Biology and Translational Science

Weiping Zheng
No abstract text is available yet for this article.
2018: Progress in Molecular Biology and Translational Science
Ning Zhang, Anthony A Sauve
NAD+ acts as a crucial regulator of cell physiology and as an integral participant in cellular metabolism. By virtue of a variety of signaling activities this central metabolite can exert profound effects on organism health status. Thus, while it serves as a well-known metabolic cofactor functioning as a redox-active substrate, it can also function as a substrate for signaling enzymes, such as sirtuins, poly (ADP-ribosyl) polymerases, mono (ADP-ribosyl) transferases, and CD38. Sirtuins function as NAD+-dependent protein deacetylases (deacylases) and catalyze the reaction of NAD+ with acyllysine groups to remove the acyl modification from substrate proteins...
2018: Progress in Molecular Biology and Translational Science
Nima Rajabi, Iacopo Galleano, Andreas S Madsen, Christian A Olsen
Lysine residues across the proteome are modified by posttranslational modifications (PTMs) that significantly enhance the structural and functional diversity of proteins. For lysine, the most abundant PTM is ɛ-N-acetyllysine (Kac), which plays numerous roles in regulation of important cellular functions, such as gene expression (epigenetic effects) and metabolism. A family of enzymes, namely histone deacetylases (HDACs), removes these PTMs. A subset of these enzymes, the sirtuins (SIRTs), represent class III HDAC and, unlike the rest of the family, these hydrolases are NAD+-dependent...
2018: Progress in Molecular Biology and Translational Science
Shengchao Li, Weiping Zheng
Sirtuins are a family of intracellular enzymes whose enzymatic activities include catalyzing the β-nicotinamide adenine dinucleotide (β-NAD+)-dependent Nɛ-acyl-lysine deacylation and the β-NAD+-dependent mono-ADP-ribosylation. Among the seven sirtuin family members (i.e., SIRT1-7) thus far identified in mammals including humans, we know SIRT1/2/3/5/6 better than SIRT4/7 as for their enzymatic activities and the cellular roles of the reactions they catalyze. This chapter will provide an updated account on the enzymology and biology of SIRT4 and SIRT7, the two less well-understood mammalian sirtuins...
2018: Progress in Molecular Biology and Translational Science
Sin Hui Neo, Bor Luen Tang
Sirtuins and their pharmacological activators/inhibitors have been associated with a range of neuroprotective effects or disease modifying influences in neurological disorders. Huntington's disease (HD) is an autosomal-dominant, progressive neurodegenerative disease characterized by movement disorder, psychiatric symptoms and cognitive decline. The monogenic mutation in HD encodes a variant of the protein Huntingtin (HTT). The disease is a consequence of a CAG repeat extension leading to an abnormally long polyglutamine (Q) stretch at HTT's N-terminus, which likely confers a toxic gain of function to the mutant polypeptide...
2018: Progress in Molecular Biology and Translational Science
Xiao Hu, Weiping Zheng
Sirtuins refer to a family of intracellular enzymes that are the yeast silent information regulator 2 (sir2) protein homologs found in organisms from all the three kingdoms of life. This family of enzymes primarily catalyze the protein Nɛ-acyl-lysine deacylation reaction despite the report for a type of bacterial/fungal sirtuins to robustly catalyze a protein mono-ADP-ribosylation reaction, however, these two group transfer reactions employ the redox coenzyme β-nicotinamide adenine dinucleotide (β-NAD+) as the obligatory cosubstrate...
2018: Progress in Molecular Biology and Translational Science
(no author information available yet)
No abstract text is available yet for this article.
January 2018: Progress in Molecular Biology and Translational Science
Carolina A Oliva, Carla Montecinos-Oliva, Nibaldo C Inestrosa
Since its discovery, Wnt signaling has been shown to be one of the most crucial morphogens in development and during the maturation of central nervous system. Its action is relevant during the establishment and maintenance of synaptic structure and neuronal function. In this chapter, we will discuss the most recent evidence on these aspects, and we will explore the evidence that involves Wnt signaling on other less known functions, such as in adult neurogenesis, in the generation of oscillatory neural rhythms, and in adult behavior...
January 2018: Progress in Molecular Biology and Translational Science
Stephanie Grainger, David Traver, Karl Willert
Leukemia and lymphoma are a wide encompassing term for a diverse set of blood malignancies that affect people of all ages and result in approximately 23,000 deaths in the United States per year (Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.). Hematopoietic stem cells (HSCs) are tissue-specific stem cells at the apex of the hierarchy that gives rise to all of the terminally differentiated blood cells, through progressively restricted progenitor populations, a process that is known to be Wnt-responsive...
January 2018: Progress in Molecular Biology and Translational Science
Elizabeth Vincan, Renate H M Schwab, Dustin J Flanagan, Jean M Moselen, Bang M Tran, Nick Barker, Toby J Phesse
The Wnt pathway is at the heart of organoid technology, which is set to revolutionize the cancer field. We can now predetermine a patient's response to any given anticancer therapy by exposing tumor organoids established from the patient's own tumor. This cutting-edge biomedical platform translates to patients being treated with the correct drug at the correct dose from the outset, a truly personalized and precise medical approach. A high throughput drug screen on organoids also allows drugs to be tested in limitless combinations...
January 2018: Progress in Molecular Biology and Translational Science
Caroline M Alexander
Attention has been focused on Wnt signaling in the mouse mammary gland for several decades, firstly by the discovery of several Wnt loci among the oncogenes revealed by MMTV-based insertional mutagenesis screening of mouse mammary gland, and then by the remarkable visualization of Wnt-dependent specification of mammary placodes in embryonic skin. This review aims to summarize the impact of recent data for our understanding of the roles of Wnt signaling in these roles. The amount and identity of both familiar and novel Wnt signaling components is examined for mouse mammary epithelial cells...
January 2018: Progress in Molecular Biology and Translational Science
Li-Shu Zhang, Lawrence Lum
Genetically based observations stemming from defects in development and in regeneration form the foundation of our understanding regarding how the secreted WNT proteins control coordinated cell fate decision-making in adult tissues. At the same time, our anticipation of potential benefits and unwanted toxicities associated with candidate anticancer agents targeting WNT signal transduction are also reliant upon this blueprint of WNT-associated physiology. Despite the long established role of WNT signaling in cancer, the emergence of WNT signaling as a suppressor of immunological attack in melanoma reveals an unanticipated anticancer potential in targeting WNT signaling...
January 2018: Progress in Molecular Biology and Translational Science
Si Hui Tan, Nick Barker
Wnt/β-catenin signaling is integral to the homeostasis and regeneration of many epithelial tissues due to its critical role in adult stem cell regulation. It is also implicated in many epithelial cancers, with mutations in core pathway components frequently present in patient tumors. In this chapter, we discuss the roles of Wnt/β-catenin signaling and Wnt-regulated stem cells in homeostatic, regenerative and cancer contexts of the intestines, stomach, skin, and liver. We also examine the sources of Wnt ligands that form part of the stem cell niche...
January 2018: Progress in Molecular Biology and Translational Science
Michael Kahn
Wnt signaling in stem cells plays critical roles in development, normal adult physiology, and disease. In this chapter, we focus on the role of the Wnt signaling pathway in somatic stem cell biology and its critical role in normal tissue homeostasis and cancer. Wnt signaling can both maintain potency and initiate differentiation in somatic stem cells, depending on the cellular and environmental context. Based principally on studies from our lab, we will explain the dichotomous behavior of this signaling pathway in determining stem cell fate decisions, placing special emphasis on the interaction of β-catenin with either of the two highly homologous Kat3 coactivator proteins, CBP and p300...
January 2018: Progress in Molecular Biology and Translational Science
Yongping Wang, Chengji J Zhou, Youhua Liu
Wnt signal cascade is an evolutionarily conserved, developmental pathway that regulates embryogenesis, injury repair, and pathogenesis of human diseases. It is well established that Wnt ligands transmit their signal via canonical, β-catenin-dependent and noncanonical, β-catenin-independent mechanisms. Mounting evidence has revealed that Wnt signaling plays a key role in controlling early nephrogenesis and is implicated in the development of various kidney disorders. Dysregulations of Wnt expression cause a variety of developmental abnormalities and human diseases, such as congenital anomalies of the kidney and urinary tract, cystic kidney, and renal carcinoma...
January 2018: Progress in Molecular Biology and Translational Science
Francesco Girardi, Fabien Le Grand
Wnt is a family of signaling molecules involved in embryogenesis, adult tissue repair, and cancer. They activate canonical and noncanonical Wnt signaling cascades in target cells. Several studies, within the last decades, showed that several Wnt ligands are involved in myogenesis and both canonical and noncanonical Wnt pathways regulate muscle formation and the maintenance of adult tissue homeostasis. In this review, we provide a comprehensive overview of the roles of Wnt signaling during muscle development and an updated description of Wnt functions during muscle repair...
January 2018: Progress in Molecular Biology and Translational Science
Astrid S Pfister, Michael Kühl
Wnt proteins are secreted glycoproteins that activate different intracellular signal transduction pathways. They regulate cell proliferation and are required for proper embryonic development. Misregulation of Wnt signaling can result in various diseases including cancer. In most circumstances, cell growth is essential for cell division and thus cell proliferation. Therefore, several reports have highlighted the key role of Wnt proteins for cell growth. Ribosomes represent the cellular protein synthesis machinery and cells need to be equipped with an appropriate number of ribosomes to allow cell growth...
January 2018: Progress in Molecular Biology and Translational Science
Bahar Degirmenci, George Hausmann, Tomas Valenta, Konrad Basler
The term "Wnt signaling" does not refer to one uniform signal transduction cascade. Instead, it describes the multiple discrete signals elicited by Wnt ligands following their interaction with distinct receptor complexes. The interaction of stem cells with niche cells is coordinated by the involvement of different signaling pathways, including Wnt signaling. The stem cell populations are highly sensitive to modulation of Wnt pathway activity. Wnt signaling is of paramount importance for stem cell self-renewal, survival, proliferation, differentiation, movement, and cell polarity...
January 2018: Progress in Molecular Biology and Translational Science
Ellen Shrock, Marc Güell
CRISPR-Cas9 has revolutionized the generation of transgenic animals. This system has demonstrated an unprecedented efficiency, multiplexability, and ease of use, thereby reducing the time and cost required for genome editing and enabling the production of animals with more extensive genetic modifications. It has also been shown to be applicable to a wide variety of animals, from early-branching metazoans to primates. Genome-wide screens in model organisms have been performed, accurate models of human diseases have been constructed, and potential therapies have been tested and validated in animal models...
2017: Progress in Molecular Biology and Translational Science
Takuro Horii, Izuho Hatada
Haploidy is a useful feature for the study of gene function because disruption of one allele in haploid cells, which contain only a single set of chromosomes, can cause loss-of-function phenotypes. Recent success in generating haploid embryonic stem (ES) cells from several mammalian species, including human, provides a new platform for simple genetic manipulation of the mammalian genome. The genome-editing potential of the CRISPR/Cas system is enhanced by the use of haploid ES cells. For example, CRISPR/Cas has been used for high-efficiency generation of multiple knockouts and knockins in haploid ES cells, with potential application in genome-wide screening...
2017: Progress in Molecular Biology and Translational Science
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