Structure-function relationships
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The TERT (telomerase reverse transcriptase) subunit of telomerase is an intensively studied macromolecule due to its key importance in maintaining genome integrity and role in cellular aging and cancer. In an effort to provide an up-to-date overview of the topic, we discuss the structure of TERT genes, their alternative splicing products and their functions. Nucleotide databases contain more than 90 full-length cDNA sequences of telomerase protein subunits. Numerous in silico, in vitro and in vivo experimental techniques have revealed a great deal of structural and functional data describing particular features of the telomerase subunit in various model organisms. We explore whether particular findings are generally applicable to telomerases or species-specific. We also discuss in an evolutionary context the role of identified functional TERT subdomains.
- MeSH
- alternativní sestřih MeSH
- eukaryotické buňky enzymologie chemie MeSH
- lidé MeSH
- molekulární evoluce MeSH
- molekulární sekvence - údaje MeSH
- prokaryotické buňky enzymologie chemie MeSH
- telomerasa genetika chemie metabolismus MeSH
- telomery metabolismus MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
The FOXO subgroup of forkhead transcription factors plays a central role in cell-cycle control, differentiation, metabolism control, stress response and apoptosis. Therefore, the function of these important molecules is tightly controlled by a wide range of protein-protein interactions and posttranslational modifications including phosphorylation, acetylation and ubiquitination. The mechanisms by which these processes regulate FOXO activity are mostly elusive. This review focuses on recent advances in structural studies of forkhead transcription factors and the insights they provide into the mechanism of DNA recognition. On the basis of these data, we discuss structural aspects of protein-protein interactions and posttranslational modifications that target the forkhead domain and the nuclear localization signal of FOXO proteins.
- MeSH
- acetylace MeSH
- financování organizované MeSH
- forkhead transkripční faktory fyziologie chemie MeSH
- fosforylace MeSH
- konformace proteinů MeSH
- lidé MeSH
- posttranslační úpravy proteinů MeSH
- ubikvitin metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
Although telomerase (EC 2.7.7.49) is important for genome stability and totipotency of plant cells, the principles of its regulation are not well understood. Therefore, we studied subcellular localization and function of the full-length and truncated variants of the catalytic subunit of Arabidopsis thaliana telomerase, AtTERT, in planta. Our results show that multiple sites in AtTERT may serve as nuclear localization signals, as all the studied individual domains of the AtTERT were targeted to the nucleus and/or the nucleolus. Although the introduced genomic or cDNA AtTERT transgenes display expression at transcript and protein levels, they are not able to fully complement the lack of telomerase functions in tert -/- mutants. The failure to reconstitute telomerase function in planta suggests a more complex telomerase regulation in plant cells than would be expected based on results of similar experiments in mammalian model systems.
- MeSH
- Arabidopsis enzymologie genetika MeSH
- buněčné jadérko enzymologie genetika MeSH
- buněčné jádro enzymologie genetika MeSH
- geneticky modifikované rostliny MeSH
- jaderné lokalizační signály genetika MeSH
- katalytická doména genetika MeSH
- listy rostlin genetika MeSH
- proteiny huseníčku genetika metabolismus MeSH
- proteosyntéza MeSH
- regulace genové exprese u rostlin MeSH
- sestřih RNA MeSH
- tabák genetika MeSH
- telomerasa chemie genetika metabolismus MeSH
- terciární struktura proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sarcoplasmic reticulum (SR) is a specialized tubular network, which not only maintains the intracellular concentration of Ca2+ at a low level but is also known to release and accumulate Ca2+ for the occurrence of cardiac contraction and relaxation, respectively. This subcellular organelle is composed of several phospholipids and different Ca2+-cycling, Ca2+-binding and regulatory proteins, which work in a coordinated manner to determine its function in cardiomyocytes. Some of the major proteins in the cardiac SR membrane include Ca2+-pump ATPase (SERCA2), Ca2+-release protein (ryanodine receptor), calsequestrin (Ca2+-binding protein) and phospholamban (regulatory protein). The phosphorylation of SR Ca2+-cycling proteins by protein kinase A or Ca2+-calmodulin kinase (directly or indirectly) has been demonstrated to augment SR Ca2+-release and Ca2+-uptake activities and promote cardiac contraction and relaxation functions. The activation of phospholipases and proteases as well as changes in different gene expressions under different pathological conditions have been shown to alter the SR composition and produce Ca2+-handling abnormalities in cardiomyocytes for the development of cardiac dysfunction. The post-translational modifications of SR Ca2+ cycling proteins by processes such as oxidation, nitrosylation, glycosylation, lipidation, acetylation, sumoylation, and O GlcNacylation have also been reported to affect the SR Ca2+ release and uptake activities as well as cardiac contractile activity. The SR function in the heart is also influenced in association with changes in cardiac performance by several hormones including thyroid hormones and adiponectin as well as by exercise-training. On the basis of such observations, it is suggested that both Ca2+-cycling and regulatory proteins in the SR membranes are intimately involved in determining the status of cardiac function and are thus excellent targets for drug development for the treatment of heart disease.
Acta physiologica Scandinavica ; Vol. 154 Supplement 624
146 s. : tab., grafy ; 24 cm
V úvodu je zdůrazněn úzký vztah mezi strukturou a funkcí, současně však i rozdílnost mezi poruchami struktury a funkce, mezi strukturální a funkční patologií: lokální vymezenost strukturál- ních poruch proti holistickému zřetězení funkčních poruch. Z hlediska vývoje je pro organismus rozhodující program, kterým se uplatňuje ve svém prostředí. Program, který se dědičně fixuje, se bezprostředně realizuje funkcí. Té se postupně přizpůsobuje struktura, která funkci umocňuje a také vymezuje, avšak opět je schopná se adaptovat měnící se funkcí (programu).
The close relationship between structure and function is first pointed out. At the same time, however, the difference between changes of structure and of function is stressed: the former is strictly localised, the latter is characterised by chain reactions affecting the entire motor system (holistic). The decisive factor from the developmental point of view is the program which enables the organism to survive. It is this program which is encoded by heredity, and makes adequate functioning possible in the first place. Structure adapts itself only gradually, but then enhances and also lim its function. If necessary, however, structure readapts itself to a change in function (program).
- MeSH
- lidé MeSH
- muskuloskeletální nemoci etiologie rehabilitace MeSH
- muskuloskeletální systém patologie MeSH
- patologie klasifikace MeSH
- pohybové poruchy etiologie rehabilitace MeSH
- rehabilitace trendy MeSH
- svaly patologie MeSH
- vývoj svalů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
