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Molecular Mechanisms of Brain Insulin Signaling 1
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Simran Chopra, Robert Hauffe, André Kleinridders
As outlined above, the insulin signaling pathway is activated through a series of phosphorylation events. As protein phosphorylation is a reversible posttranslational modification, it represents a readily available site for fine-tuning the amplitude of the signaling response as well as a site for a negative feedback loop. Enzymatic dephosphorylation is carried out by phosphatases. In the case of the insulin signaling pathway, we can differentiate between two cases: (i) dephosphorylation of proteins in a negative feedback loop to stop the signaling cascade and (ii) inhibitory phosphorylation of proteins to limit the intensity of the cellular response to insulin (Figure 1.3).
Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Sujatha Puttalingaiah, Murthy V. Greeshma, Mahadevaswamy G. Kuruburu, Venugopal R. Bovilla, SubbaRao V. Madhunapantula
Modification of histones by acetylation is one of the most common post-translational modifications, and was first defined in 1960. Inoue and Fujimoto (1969) observed that acetyl groups are removed from the histones in a calf thymus extract. Subsequently, during the 1970s, several studies identified HDAC activity in tissues; and in 1996, the first bona fide histone deacetylase, i.e. HDAC1, was isolated and cloned (Taunton et al., 1996). HDACs remove acetyl groups from histones, resulting in a more condensed, transcriptionally inactive chromatin state. Inactive chromatin causes the downregulation of tumor suppressor genes such as p21, p27, p53 and (retinoblastoma protein) Rb, etc., leading to uncontrolled cell proliferation, survival, migration and differentiation (Figure 8.2) (Parbin et al., 2014). Therefore, hyper-active HDACs are reported to induce cancer (Li and Seto, 2016). A number of studies further dissected the biochemical characterization of the histone deacetylase and elucidated structure–activity relationships.
Genetics and exercise: an introduction
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Claude Bouchard, Henning Wackerhage
You probably wonder about the 5’ and 3’ ends, and the “AAA” annotation at the end of the mRNA sequence. The 5’ and 3’ refer to the position of specific carbon atoms in the deoxyribose sugar of a DNA strand and provide information about the direction of the DNA strand. The “AAA” symbolizes the so-called poly-A tail added to each mRNA after transcription, which makes RNA more stable. Transcription of RNA takes place in the nucleus of the cell, whilst translation of proteins in the ribosomes occur in the cytoplasm. Once translated into a polypeptide, posttranslational modifications such as phosphorylation, methylation or acetylation may happen to generate a mature, functional protein or change how active the protein is.
The role of N-myristoyltransferase 1 in tumour development
Published in Annals of Medicine, 2023
Hong Wang, Xin Xu, Jiayi Wang, Yongxia Qiao
Tumourigenesis is characterized by biological properties such as sustained proliferation, resistance to apoptosis, metastasis, epithelial mesenchymal transition, metabolic reprogramming and immune escape [1], and is caused by altered activity of intracellular signalling, metabolic and gene regulatory networks. Protein post-translational modifications are tightly associated with in these alterations [2–4]. Protein post-translational modifications are covalent attachments of specific motifs to amino acid residues of proteins under the catalytic action of enzymes. Typical post-translational modifications are methylation, phosphorylation, ubiquitination and lipidation [4]. In recent years, the importance of one of these lipid modifications, myristoylation, in the development of human tumourigenesis has emerged [5,6]. A series of studies has shown that myristoylation plays an essential role in signal transduction, protein stability and protein localization at the membrane [7].
SUMO-specific protease 1 inhibitors–A literature and patent overview
Published in Expert Opinion on Therapeutic Patents, 2022
Hang Li, Leyuan Chen, Yiliang Li, Wenbin Hou
SUMOylation is a post-translational modification and is involved in various crucial functions of cells, such as regulation of the cell cycle, DNA damage repair, apoptosis, etc [13,14]. SUMOylation is a dynamic and reversible enzymatic cascade reaction process. Several enzymes are involved in this process, including activating enzyme E1, conjugating enzyme E2, and ligase enzyme E3. The SUMOylation process includes four phases: maturation, activation, conjugation and ligation. Firstly, SUMO-specific protease cuts several amino acids at the carboxyl terminal of the SUMO precursor protein, and exposes the diglycine residues to mature SUMO protein. Afterward, the mature SUMO protein is linked with cysteine of the activating enzyme E1 through a thiolipid bond, forming SUMO-E1 complex. SUMO protein is then transferred to conjugating enzyme E2. Finally, under the action of ligase E3, SUMO is transferred from E2 to the lysine residue of the substrate protein, which was connected with substrate protein by an isopeptide bond (Figure 1) [15,16].
Inhibition of O-glycosylation aggravates GalN/LPS-induced liver injury through activation of ER stress
Published in Immunopharmacology and Immunotoxicology, 2021
Dongkui Xu, Zhenguo Zhao, Yixian Li, Chao Shang, Lijie Liu, Jiaxu Yan, Ying Zheng, Zongmei Wen, Tao Gu
Glycosylation is the enzymatic addition of carbohydrate chains to proteins, which is the most common post-translational modification on many membrane-associated and secreted proteins [1,2]. Glycosylation can significantly affect a variety of fundamental biological processes [3]. According to sugar-amino acid linkages, glycosylation can be divided into two major types: N-glycosylation (Asn-linked) and O-glycosylation (Ser/Thr-linked) [4]. N-glycosylation is well-studied and predictable, whereas O-glycosylation is more complex and less elucidated [5]. O-glycosylation is essential for protein function, including protein structure, folding, stability, localization, and recognition, etc., and can also modulate enzyme activity and cell-to-cell and cell-to-extracellular matrix (ECM) interactions [6,7]. Many carcinomas exhibit aberrant O-glycosylation and produce truncated O-glycans, such as Tn/STn antigen [8,9]. Pathological exposure of Tn antigen on the cell surface or secreted proteins may promote cancer progression and metastasis [9–11]. In addition, aberrant O-glycosylation may play a role in systemic inflammation, ranging from leukocyte trafficking to initiation of innate immunity, which manifests as pro- or anti-inflammatory effects under certain conditions [12–14]. So far the specific functions of O-glycosylation during inflammation remain to be determined. Understanding the molecular mechanisms of O-glycosylation in the regulation of inflammation may lead to a greater appreciation of the related diseases involving altered O-glycosylation.