scholarly journals The governor: Protein phosphorylation

2007 ◽  
Vol 29 (4) ◽  
pp. 20-23 ◽  
Author(s):  
Dario R. Alessi and Elton Zeqiraj

At first glance, the odds that the introduction of a diminutive and unsuspicious phosphoryl group on to a hydroxycontaining side chain of a much larger protein molecule would be selected by Nature as the most widely deployed mechanism to control biological processes, and be responsible for many major diseases, seems unlikely. However, this process termed protein phosphorylation is a vital regu lator of almost all events that take place in eukaryotic organisms. In this review we will outline what phosphorylation is, how it is regulated and why disruptions of the network of enzymes and proteins that regulate the phosphorylation are a principal cause of many maladies. We will also discuss how advances are leading to exciting strategies to develop drugs to treat diseases caused by disruptions of protein phosphorylation.

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1632
Author(s):  
Ulrich-Axel Bommer ◽  
Adam Telerman

Translationally controlled tumor protein (TCTP), also called histamine releasing factor (HRF) or fortilin, is a multifunctional protein present in almost all eukaryotic organisms. TCTP is involved in a range of basic cell biological processes, such as promotion of growth and development, or cellular defense in response to biological stresses. Cellular TCTP levels are highly regulated in response to a variety of physiological signals, and regulatory mechanism at various levels have been elucidated. Given the importance of TCTP in maintaining cellular homeostasis, it is not surprising that dysregulation of this protein is associated with a range of disease processes. Here, we review recent progress that has been made in the characterisation of the basic biological functions of TCTP, in the description of mechanisms involved in regulating its cellular levels and in the understanding of dysregulation of TCTP, as it occurs in disease processes such as cancer.


2021 ◽  
Vol 22 (9) ◽  
pp. 4349
Author(s):  
Eri Chatani ◽  
Keisuke Yuzu ◽  
Yumiko Ohhashi ◽  
Yuji Goto

Amyloid fibrils are supramolecular protein assemblies represented by a cross-β structure and fibrous morphology, whose structural architecture has been previously investigated. While amyloid fibrils are basically a main-chain-dominated structure consisting of a backbone of hydrogen bonds, side-chain interactions also play an important role in determining their detailed structures and physicochemical properties. In amyloid fibrils comprising short peptide segments, a steric zipper where a pair of β-sheets with side chains interdigitate tightly is found as a fundamental motif. In amyloid fibrils comprising longer polypeptides, each polypeptide chain folds into a planar structure composed of several β-strands linked by turns or loops, and the steric zippers are formed locally to stabilize the structure. Multiple segments capable of forming steric zippers are contained within a single protein molecule in many cases, and polymorphism appears as a result of the diverse regions and counterparts of the steric zippers. Furthermore, the β-solenoid structure, where the polypeptide chain folds in a solenoid shape with side chains packed inside, is recognized as another important amyloid motif. While side-chain interactions are primarily achieved by non-polar residues in disease-related amyloid fibrils, the participation of hydrophilic and charged residues is prominent in functional amyloids, which often leads to spatiotemporally controlled fibrillation, high reversibility, and the formation of labile amyloids with kinked backbone topology. Achieving precise control of the side-chain interactions within amyloid structures will open up a new horizon for designing useful amyloid-based nanomaterials.


ChemInform ◽  
2008 ◽  
Vol 39 (34) ◽  
Author(s):  
P. S. Lemport ◽  
G. V. Bodrin ◽  
M. P. Pasechnik ◽  
A. G. Matveeva ◽  
P. V. Petrovskii ◽  
...  
Keyword(s):  

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324554
Author(s):  
Dina Kremsdorf ◽  
Bouchra Lekbaby ◽  
Pierre Bablon ◽  
Jules Sotty ◽  
Jérémy Augustin ◽  
...  

Regulation of alternative splicing is one of the most efficient mechanisms to enlarge the proteomic diversity in eukaryotic organisms. Many viruses hijack the splicing machinery following infection to accomplish their replication cycle. Regarding the HBV, numerous reports have described alternative splicing events of the long viral transcript (pregenomic RNA), which also acts as a template for viral genome replication. Alternative splicing of HBV pregenomic RNAs allows the synthesis of at least 20 spliced variants. In addition, almost all these spliced forms give rise to defective particles, detected in the blood of infected patients. HBV-spliced RNAs have long been unconsidered, probably due to their uneasy detection in comparison to unspliced forms as well as for their dispensable role during viral replication. However, recent data highlighted the relevance of these HBV-spliced variants through (1) the trans-regulation of the alternative splicing of viral transcripts along the course of liver disease; (2) the ability to generate defective particle formation, putative biomarker of the liver disease progression; (3) modulation of viral replication; and (4) their intrinsic propensity to encode for novel viral proteins involved in liver pathogenesis and immune response. Altogether, tricky regulation of HBV alternative splicing may contribute to modulate multiple viral and cellular processes all along the course of HBV-related liver disease.


2021 ◽  
Vol 22 (19) ◽  
pp. 10285
Author(s):  
Pietro Laneve ◽  
Paolo Tollis ◽  
Elisa Caffarelli

RNA metabolism is central to cellular physiopathology. Almost all the molecular pathways underpinning biological processes are affected by the events governing the RNA life cycle, ranging from transcription to degradation. The deregulation of these processes contributes to the onset and progression of human diseases. In recent decades, considerable efforts have been devoted to the characterization of noncoding RNAs (ncRNAs) and to the study of their role in the homeostasis of the nervous system (NS), where they are highly enriched. Acting as major regulators of gene expression, ncRNAs orchestrate all the steps of the differentiation programs, participate in the mechanisms underlying neural functions, and are crucially implicated in the development of neuronal pathologies, among which are neurodegenerative diseases. This review aims to explore the link between ncRNA dysregulation and amyotrophic lateral sclerosis (ALS), the most frequent motoneuron (MN) disorder in adults. Notably, defective RNA metabolism is known to be largely associated with this pathology, which is often regarded as an RNA disease. We also discuss the potential role that these transcripts may play as diagnostic biomarkers and therapeutic targets.


2008 ◽  
Vol 36 (6) ◽  
pp. 1112-1119 ◽  
Author(s):  
Sibali Bandyopadhyay ◽  
Kala Chandramouli ◽  
Michael K. Johnson

Iron–sulfur (Fe–S) clusters are present in more than 200 different types of enzymes or proteins and constitute one of the most ancient, ubiquitous and structurally diverse classes of biological prosthetic groups. Hence the process of Fe–S cluster biosynthesis is essential to almost all forms of life and is remarkably conserved in prokaryotic and eukaryotic organisms. Three distinct types of Fe–S cluster assembly machinery have been established in bacteria, termed the NIF, ISC and SUF systems, and, in each case, the overall mechanism involves cysteine desulfurase-mediated assembly of transient clusters on scaffold proteins and subsequent transfer of pre-formed clusters to apo proteins. A molecular level understanding of the complex processes of Fe–S cluster assembly and transfer is now beginning to emerge from the combination of in vivo and in vitro approaches. The present review highlights recent developments in understanding the mechanism of Fe–S cluster assembly and transfer involving the ubiquitous U-type scaffold proteins and the potential roles of accessory proteins such as Nfu proteins and monothiol glutaredoxins in the assembly, storage or transfer of Fe–S clusters.


2008 ◽  
Vol 36 (4) ◽  
pp. 684-689 ◽  
Author(s):  
Ian Brierley ◽  
Robert J.C. Gilbert ◽  
Simon Pennell

RNA pseudoknots are structural elements found in almost all classes of RNA. Pseudoknots form when a single-stranded region in the loop of a hairpin base-pairs with a stretch of complementary nucleotides elsewhere in the RNA chain. This simple folding strategy is capable of generating a large number of stable three-dimensional folds that display a diverse range of highly specific functions in a variety of biological processes. The present review focuses on pseudoknots that act in the regulation of protein synthesis using cellular and viral examples to illustrate their versatility. Emphasis is placed on structurally well-defined pseudoknots that play a role in internal ribosome entry, autoregulation of initiation, ribosomal frameshifting during elongation and trans-translation.


2020 ◽  
Vol 18 (2) ◽  
pp. 91-114
Author(s):  
Vladimir I. Vashchenko ◽  
Petr D. Shabanov

Extracellular vesicles (EVs) represent heterogeneous population of the microparticles liberated by almost all live cages which are widely investigated recently in various biological and medical areas. They usually consist of two basic types (exosomes and microvesicles) and recently draw the increasing attention in quality mesenges of the cellular alarm system. Really, these vesicles can influence on cages-recipients, transferring and delivering difficult complexes of biomolecules (the lipids, proteins, coagulation factors, antigene, nucleinic acids), protected from enzymatic to degradation in environment. Importance EVs has been shown in pathophysiology several bodies, in particular, in kidneys where various types of cages нефрона allocate EVs which mediate their communication with underlaying cages urinogenous ways. By numerous researches it is established that EVs are involved in cellular communications during the regenerative and pathological processes occurring in a kidney. During the last years also it has been proved that vesicles play an important role in normal physiology of kidneys. Though many mechanisms EVs at illnesses are still studied insufficiently, in particular, in kidneys, opening of a role of additional mechanisms can help to throw light on the biological processes proceeding in kidneys. Eventually, extracellular vesicles, allocated with nephritic cages, collect in urine, becoming, thus, the big resource as markers of illnesses urinogenous a path and the perspective noninvasive diagnostic tool at nephritic illnesses. In the present review we discuss the latest data about a role EVs in pathophysiology of kidneys and their potential prospects in diagnostics and therapy of nephritic illness.


2007 ◽  
Vol 56 (9) ◽  
pp. 1911-1917 ◽  
Author(s):  
P. S. Lemport ◽  
G. V. Bodrin ◽  
M. P. Pasechnik ◽  
A. G. Matveeva ◽  
P. V. Petrovskii ◽  
...  
Keyword(s):  

2009 ◽  
Vol 425 (2) ◽  
pp. 295-302 ◽  
Author(s):  
Victoria H. Cowling

The 7-methylguanosine cap added to the 5′ end of mRNA is essential for efficient gene expression and cell viability. Methylation of the guanosine cap is necessary for the translation of most cellular mRNAs in all eukaryotic organisms in which it has been investigated. In some experimental systems, cap methylation has also been demonstrated to promote transcription, splicing, polyadenylation and nuclear export of mRNA. The present review discusses how the 7-methylguanosine cap is synthesized by cellular enzymes, the impact that the 7-methylguanosine cap has on biological processes, and how the mRNA cap methylation reaction is regulated.


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