China
Africa
Explore chapters and articles related to this topic
Diagnosis and Pathobiology
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
The most widely studied eukaryotic PTM is phosphorylation because of its involvement in a broad range of cellular functions connecting various enzymes or receptors [368]. Phosphorylation involves a chemical reaction where a phosphate group is transferred from the γ-locus of adenosine triphosphate (ATP) or guanosine 5′-triphosphate to the side chain of an amino acid residue of a protein or substrate (commonly on serine, threonine, and tyrosine residues) [368]. Protein kinase catalysis mediates these reactions and phosphatase enzymes catalyze dephosphorylation [368, 387]. Histone phosphorylation sites mostly lie on the N-terminal tails, but particular core regions can also be phosphorylated (e.g., nonreceptor tyrosine kinase JAK2 involved in cancer) [387, 395].
The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
Cells can use extracellular molecules to communicate with one another. Signal transduction pathways translate these stimuli into an appropriate cellular response, usually through a series of phosphorylation reactions leading to novel gene transcription in the nucleus. Signalling pathways play a role in the development of many cancers.
Chronic Traumatic Encephalopathy
Published in Alexander R. Toftness, Incredible Consequences of Brain Injury, 2023
Researchers think that one of the big reasons that tau stops hugging microtubules is because getting hit in the head damages these tiny structures and causes the tau to become detached (VanItallie, 2019). It's a very literal hypothesis: concussive and subconcussive blows to the head knock tau loose. Sometimes, especially when detached from microtubules, a bunch of phosphate molecules will attach to the tau protein and more or less weigh it down and prevent it from doing its job. When many phosphate molecules are attached to tau, it is known as hyperphosphorylated tau, which is generally shortened to p-tau (Bieniek et al., 2021). Phosphorylation is also normal in the brain—it is a common way that proteins help to regulate cellular processes. The reason that p-tau gets so much attention is that there appear to be good and evil versions.
Effects of MFG-E8 expression on the biological characteristics of ovarian cancer cells via the AKT/mTOR/S6K signalling pathway
Published in Journal of Obstetrics and Gynaecology, 2023
Na Li, Yazhuo Wang, Lin Liu, Pei Wang, Xiaohua Wu
Phosphorylated proteins are the main mediators of intracellular signal transduction. Phosphorylation not only activates proteins but also amplifies the transmitted signals and induces biological responses both inside and outside the cell. The AKT/mTOR/S6K signalling pathway, which is an important signal transduction pathway in cells, is involved in various aspects of cell growth, proliferation, and metabolic regulation. Abnormal functioning of this pathway can cause developmental defects and metabolic diseases, in addition to promoting tumour formation (Khan et al.2013, Li et al.2019). In another study, MFG-E8 was reported to be an important activator of the AKT pathway (Zhao et al.2017). Here, we found that MFG-E8 silencing in SKOV3 cells inhibited not only AKT phosphorylation but also the phosphorylation of mTOR and its downstream S6K, suggesting that MFG-E8 may participate in the biological functions of tumour cells by regulating the mTOR/S6K signalling pathway.
COVID-19: a wreak havoc across the globe
Published in Archives of Physiology and Biochemistry, 2023
Heena Rehman, Md Iftekhar Ahmad
The N protein has two separate domains, namely the N terminal domain and C terminal domain. The N protein in different viruses uses different mechanisms for binding to the RNA. The N terminal domain is heavily phosphorylated. It binds to the viral genome in beads on a string manner. There are basically two substrates of N protein. One of the substrates is the trinucleotide repeat sequence (TRSs) which binds to the C terminus and other substrate binds to the genomic packaging signal. The gene coding for N protein precedes the 3′UTR of the coronavirus genome (Rota et al.2003). Nucleocapsid is involved in viral packaging, viral core formation, and vRNA synthesis (Hiscox et al.2001). The N protein of novel coronavirus consist of a short lysine rich region (KTFPPTEPKKDKKKKTDEAQ) near the C terminal which is unique (Marra et al. 2003). It is speculated that this region acts as a nuclear localising region which allows N protein to enter the nucleus through passive diffusion (Rowland et al.1999). It gets phosphorylated after translation. The phosphorylation allows it to enter the nucleus at specific stages of the cell cycle (Hiscox et al.2001). During the interphase, the N protein gets an opportunity to interact with various transcription factors and regulatory complexes. N protein affects the signal transduction pathways resulting in inflammation, apoptosis, and several other cellular processes.
Synthesis, biological evaluation, and in silico studies of new CDK2 inhibitors based on pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffold with apoptotic activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Asmaa A. Mandour, Ibrahim F. Nassar, Mohammed T. Abdel Aal, Mahmoud A. E. Shahin, Wael A. El-Sayed, Maghawry Hegazy, Amr Mohamed Yehia, Ahmed Ismail, Mohamed Hagras, Eslam B. Elkaeed, Hanan M. Refaat, Nasser S. M. Ismail
Protein kinases represent a large group of structurally related enzymes that are essential and regulate cell cycle progression involved in cell division1–3. Cyclin-dependent kinases (CDKs) are serine-threonine kinases responsible for cell cycle regulation and cell differentiation2. Cyclin-dependent kinases (CDK) are mainly responsible for the phosphorylation process of proteins4–6. Cyclin is the regulatory protein bound by CDK leading to ATP binding region modification2. CDKs in absence of cyclin have less activity where the activation loop (known as T-loop) blocks the cleft, and the key amino acid residues are not optimally positioned for ATP binding2. CDK2 has a catalytic effect in cyclin-dependent protein kinase complex7,8. Protein phosphorylation has a critical role in cellular function regulation. This essential role during the cell cycle could be altered in tumour cells7–11. Alteration in kinases may lead to the development of many diseases, including cancer. Hence, the control of CDK dependent cell cycle is essential for tumour progression management. Where overexpression of CDK enzymes occurs in cancer2. As uncontrolled CDK2 activation in human cancer is associated with overexpression of cyclins A and E in many human cancers12. Thus, CDKs are considered critical targets for the development of novel anticancer drugs9,10.