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Critical Reviews in Biochemistry and Molecular Biology

Shafqat Rasool, Jean-François Trempe
Mutations in PINK1 cause early-onset recessive Parkinson's disease. This gene encodes a protein kinase implicated in mitochondrial quality control via ubiquitin phosphorylation and activation of the E3 ubiquitin ligase Parkin. Here, we review and analyze functional features emerging from recent crystallographic, nuclear magnetic resonance (NMR) and mass spectrometry studies of PINK1. We compare the apo and ubiquitin-bound PINK1 structures and reveal an allosteric switch, regulated by autophosphorylation, which modulates substrate recognition...
September 21, 2018: Critical Reviews in Biochemistry and Molecular Biology
Neel H Shah, Jeanine F Amacher, Laura M Nocka, John Kuriyan
Tyrosine kinases were first discovered as the protein products of viral oncogenes. We now know that this large family of metazoan enzymes includes nearly one hundred structurally diverse members. Tyrosine kinases are broadly classified into two groups: the transmembrane receptor tyrosine kinases, which sense extracellular stimuli, and the cytoplasmic tyrosine kinases, which contain modular ligand-binding domains and propagate intracellular signals. Several families of cytoplasmic tyrosine kinases have in common a core architecture, the "Src module," composed of a Src-homology 3 (SH3) domain, a Src-homology 2 (SH2) domain, and a kinase domain...
September 5, 2018: Critical Reviews in Biochemistry and Molecular Biology
Robert M Hughes
On-cue regulation of gene transcription is an invaluable tool for the study of biological processes and the development and integration of next-generation therapeutics. Ideal reagents for the precise regulation of gene transcription should be nontoxic to the host system, highly tunable, and provide a high level of spatial and temporal control. Light, when coupled with protein or small molecule-linked photoresponsive elements, presents an attractive means of meeting the demands of an ideal system for regulating gene transcription...
July 24, 2018: Critical Reviews in Biochemistry and Molecular Biology
Stéphanie Lebreton, Chiara Zurzolo, Simona Paladino
Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are a class of proteins attached to the extracellular leaflet of the plasma membrane via a post-translational modification, the glycolipid anchor. The presence of both glycolipid anchor and protein portion confers them unique features. GPI-APs are expressed in all eukaryotes, from fungi to plants and animals. They display very diverse functions ranging from enzymatic activity, signaling, cell adhesion, cell wall metabolism, neuritogenesis, and immune response...
August 2018: Critical Reviews in Biochemistry and Molecular Biology
María-Eugenia Zaballa, F Gisou van der Goot
S-Acylation (commonly referred to as S-palmitoylation) is a post-translational modification consisting in the covalent attachment of an acyl chain to a cysteine residue of the target protein. The lability of the resulting thioester bond gives S-acylation an essential characteristic: its reversibility. S-acylation dynamically regulates different aspects in the life of a protein (including stability, localization, interactome, and function) and, thus, plays critical roles in cellular physiology. For long, the reversibility of S-acylation has been neglected and thereby its potential as a regulatory mechanism for protein function undervalued...
August 2018: Critical Reviews in Biochemistry and Molecular Biology
Alexandra Vaisman, Roger Woodgate
The well-being of all living organisms relies on the accurate duplication of their genomes. This is usually achieved by highly elaborate replicase complexes which ensure that this task is accomplished timely and efficiently. However, cells often must resort to the help of various additional "specialized" DNA polymerases that gain access to genomic DNA when replication fork progression is hindered. One such specialized polymerase family consists of the so-called "translesion synthesis" (TLS) polymerases; enzymes that have evolved to replicate damaged DNA...
August 2018: Critical Reviews in Biochemistry and Molecular Biology
Cassandra S Carroll, Margo M Moore
Iron is required for microbial growth and proliferation. To survive in low-iron environments, some microorganisms secrete ferric iron chelators called siderophores. Siderophore biosynthesis occurs via two pathways: the non-ribosomal peptide synthetase (NRPS) pathway and the NRPS-independent siderophore (NIS) synthetase pathway. NIS enzymes function by adenylating a carboxylic acid substrate, typically citrate, or a derivative, followed by nucleophilic capture of an amine or alcohol and displacement of a citryl intermediate...
August 2018: Critical Reviews in Biochemistry and Molecular Biology
Hong-Leong Cheah, Carsten A Raabe, Li-Pin Lee, Timofey S Rozhdestvensky, Marimuthu Citartan, Siti Aminah Ahmed, Thean-Hock Tang
Over the past decade, RNA-deep sequencing has uncovered copious non-protein coding RNAs (npcRNAs) in bacteria. Many of them are key players in the regulation of gene expression, taking part in various regulatory circuits, such as metabolic responses to different environmental stresses, virulence, antibiotic resistance, and host-pathogen interactions. This has contributed to the high adaptability of bacteria to changing or even hostile environments. Their mechanisms include the regulation of transcriptional termination, modulation of translation, and alteration of messenger RNA (mRNA) stability, as well as protein sequestration...
August 2018: Critical Reviews in Biochemistry and Molecular Biology
Angela Jeong, Kiall Francis Suazo, W Gibson Wood, Mark D Distefano, Ling Li
The mevalonate-isoprenoid-cholesterol biosynthesis pathway plays a key role in human health and disease. The importance of this pathway is underscored by the discovery that two major isoprenoids, farnesyl and geranylgeranyl pyrophosphate, are required to modify an array of proteins through a process known as protein prenylation, catalyzed by prenyltransferases. The lipophilic prenyl group facilitates the anchoring of proteins in cell membranes, mediating protein-protein interactions and signal transduction...
June 2018: Critical Reviews in Biochemistry and Molecular Biology
Surinder Kumar, David B Lombard
Sirtuins are NAD+ -dependent protein deacylases/ADP-ribosyltransferases that have emerged as candidate targets for new therapeutics to treat metabolic disorders and other diseases, including cancer. The sirtuin SIRT5 resides primarily in the mitochondrial matrix and catalyzes the removal of negatively charged lysine acyl modifications; succinyl, malonyl, and glutaryl groups. Evidence has now accumulated to document the roles of SIRT5 as a significant regulator of cellular homeostasis, in a context- and cell-type specific manner, as has been observed previously for other sirtuin family members...
June 2018: Critical Reviews in Biochemistry and Molecular Biology
Claire L Smillie, Tamara Sirey, Chris P Ponting
Control of gene and protein expression is required for cellular homeostasis and is disrupted in disease. Following transcription, mRNA turnover and translation is modulated, most notably by microRNAs (miRNAs). This modulation is controlled by transcriptional and post-transcriptional events that alter the availability of miRNAs for target binding. Recent studies have proposed that some transcripts - termed competitive endogenous RNAs (ceRNAs) - sequester a miRNA and diminish its repressive effects on other transcripts...
June 2018: Critical Reviews in Biochemistry and Molecular Biology
Federica Iavarone, Claudia Desiderio, Alberto Vitali, Irene Messana, Claudia Martelli, Massimo Castagnola, Tiziana Cabras
Proteomic surveys with top-down platforms are today revealing thousands of naturally occurring fragments of bigger proteins. Some of them have not functional meaning because they derive from pathways responsible for protein degradation, but many have specific functions, often completely different from that one of the parent proteins. These peptides encrypted in the protein sequence are nowadays called cryptides. They are frequent in the animal and plant kingdoms and represent a new interesting -omic field of investigation...
June 2018: Critical Reviews in Biochemistry and Molecular Biology
Mariana Verdelho Machado, Anna Mae Diehl
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of obesity-associated liver diseases and it has become the major cause of cirrhosis in the Western world. The high prevalence of NAFLD-associated advanced liver disease reflects both the high prevalence of obesity-related fatty liver (hepatic steatosis) and the lack of specific treatments to prevent hepatic steatosis from progressing to more serious forms of liver damage, including nonalcoholic steatohepatitis (NASH), cirrhosis, and primary liver cancer...
June 2018: Critical Reviews in Biochemistry and Molecular Biology
Alexandra C Newton
Protein kinase C (PKC) isozymes belong to a family of Ser/Thr kinases whose activity is governed by reversible release of an autoinhibitory pseudosubstrate. For conventional and novel isozymes, this is effected by binding the lipid second messenger, diacylglycerol, but for atypical PKC isozymes, this is effected by binding protein scaffolds. PKC shot into the limelight following the discovery in the 1980s that the diacylglycerol-sensitive isozymes are "receptors" for the potent tumor-promoting phorbol esters...
April 2018: Critical Reviews in Biochemistry and Molecular Biology
Saeideh Nakhaei-Rad, Fereshteh Haghighi, Parivash Nouri, Soheila Rezaei Adariani, Jana Lissy, Neda S Kazemein Jasemi, Radovan Dvorsky, Mohammad Reza Ahmadian
No abstract text is available yet for this article.
April 2018: Critical Reviews in Biochemistry and Molecular Biology
Stella M Lu, Gregory D Fairn
The plasma membrane is compartmentalized into several distinct regions or domains, which show a broad diversity in both size and lifetime. The segregation of lipids and membrane proteins is thought to be driven by the lipid composition itself, lipid-protein interactions and diffusional barriers. With regards to the lipid composition, the immiscibility of certain classes of lipids underlies the "lipid raft" concept of plasmalemmal compartmentalization. Historically, lipid rafts have been described as cholesterol and (glyco)sphingolipid-rich regions of the plasma membrane that exist as a liquid-ordered phase that are resistant to extraction with non-ionic detergents...
April 2018: Critical Reviews in Biochemistry and Molecular Biology
Shahienaz E Hampton, Timothy M Dore, Walter K Schmidt
Ras converting enzyme 1 (Rce1) is an integral membrane endoprotease localized to the endoplasmic reticulum that mediates the cleavage of the carboxyl-terminal three amino acids from CaaX proteins, whose members play important roles in cell signaling processes. Examples include the Ras family of small GTPases, the γ-subunit of heterotrimeric GTPases, nuclear lamins, and protein kinases and phosphatases. CaaX proteins, especially Ras, have been implicated in cancer, and understanding the post-translational modifications of CaaX proteins would provide insight into their biological function and regulation...
April 2018: Critical Reviews in Biochemistry and Molecular Biology
Jacqueline Howie, Krzysztof J Wypijewski, Fiona Plain, Lindsay B Tulloch, Niall J Fraser, William Fuller
The ubiquitous sodium/potassium ATPase (Na pump) is the most abundant primary active transporter at the cell surface of multiple cell types, including ventricular myocytes in the heart. The activity of the Na pump establishes transmembrane ion gradients that control numerous events at the cell surface, positioning it as a key regulator of the contractile and metabolic state of the myocardium. Defects in Na pump activity and regulation elevate intracellular Na in cardiac muscle, playing a causal role in the development of cardiac hypertrophy, diastolic dysfunction, arrhythmias and heart failure...
April 2018: Critical Reviews in Biochemistry and Molecular Biology
Yajie Wang, Hengqian Ren, Huimin Zhao
Biocatalysts have been increasingly used in the synthesis of fine chemicals and medicinal compounds due to significant advances in enzyme discovery and engineering. To mimic the synergistic effects of cascade reactions catalyzed by multiple enzymes in nature, researchers have been developing artificial tandem enzymatic reactions in vivo by harnessing synthetic biology and metabolic engineering tools. There is also growing interest in the development of one-pot tandem enzymatic or chemo-enzymatic processes in vitro due to their neat and concise catalytic systems and product purification procedures...
April 2018: Critical Reviews in Biochemistry and Molecular Biology
Zintis Inde, Scott J Dixon
The goal of cancer chemotherapy is to induce homogeneous cell death within the population of targeted cancer cells. However, no two cells are exactly alike at the molecular level, and sensitivity to drug-induced cell death, therefore, varies within a population. Genetic alterations can contribute to this variability and lead to selection for drug resistant clones. However, there is a growing appreciation for the role of non-genetic variation in producing drug-tolerant cellular states that exhibit reduced sensitivity to cell death for extended periods of time, from hours to weeks...
February 2018: Critical Reviews in Biochemistry and Molecular Biology
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