China
Africa
Explore chapters and articles related to this topic
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
Variations in the levels of HAT and HDAC influence the compaction of chromatin, thereby causing improper expression of specific genes and culminating in genomic instability and epigenetic diseases (Park and Kim, 2020). Mechanistically, the amino groups of lysine residues in a protein undergoing different post-translational modifications such as acetylation, methylation, ubiquitination, sumoylation, propionylation, butyrylation, crotonylation, etc., thereby influencing the expression of genes (Seto and Yoshida, 2014). Class I HDACs play a prominent role in cell survival and proliferation, whereas Class II HDACs exhibit tissue-specific functions (Morris and Monteggia, 2013). For instance, HDAC1 knockout cells have a general proliferation and survival defect, despite increased levels of HDAC2 and HDAC3 activity. HDAC2 modulates transcriptional activity by regulating p53 binding. Abnormal HDACs play a key role in many human diseases including cancer, neurological and metabolic disorders, and inflammatory, cardiac and pulmonary diseases.
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].
Open resources for chemical probes and their implications for future drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Esra Balıkçı, Anne-Sophie M. C. Marques, Jesper S. Hansen, Kilian V. M. Huber
Ubiquitination is the second most observed posttranslational modification in human proteins [70]. This process involves the cooperative activity of E1, E2, and E3 enzymes to tag protein substrates with ubiquitin chains to induce their proteasomal degradation. Components of the ubiquitin system are attractive therapeutic targets since aberrations in this process have been associated with many diseases such as cancer and neurodegeneration [71,72]. Several UPS-targeting small molecules have been approved or are undergoing clinical trials (see literature for relevant reviews, such as [73]). The best characterized E3 ligase modulators include thalidomide and its derivatives lenalidomide and pomalidomide, also called immunomodulatory drugs (ImiDs), which are approved for the treatment of multiple myeloma. These compounds enable surface remodeling of the E3 ligase substrate receptor cereblon (CRBN), altering its affinity for preferred substrates. Subsequent modifications to these so-called molecular glues yielded compounds with greater selectivity and a broader range of compatible substrates [74–76]. Aside from their therapeutic value, these drugs have paved the way for the emerging area of targeted protein degradation (TPD), highlighting the vast potential of proximity-induced pharmacology [77–79].
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].