Human and Arabidopsis alpha-ketoglutarate-dependent dioxygenase homolog proteins-New players in important regulatory processes
Autor: | Dorota Łucja Zugaj, Jaroslaw Steciuk, Tomaš Pilžys, Michał Marcinkowski, Damian Mielecki, Elżbieta Grzesiuk, Damian Garbicz, Tomasz J. Sarnowski |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Clinical Biochemistry AlkB Arabidopsis Alpha-Ketoglutarate-Dependent Dioxygenase FTO Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics Arabidopsis thaliana Humans Phosphorylation Molecular Biology Messenger RNA biology Arabidopsis Proteins RNA AlkB Homolog 5 RNA Demethylase RNA-Binding Proteins Oxidoreductases N-Demethylating Cell Biology biology.organism_classification Protein ubiquitination Cell biology 030104 developmental biology chemistry 030220 oncology & carcinogenesis biology.protein Demethylase DNA |
Zdroj: | IUBMB lifeREFERENCES. 72(6) |
ISSN: | 1521-6551 |
Popis: | The family of AlkB homolog (ALKBH) proteins, the homologs of Escherichia coli AlkB 2-oxoglutarate (2OG), and Fe(II)-dependent dioxygenase are involved in a number of important regulatory processes in eukaryotic cells including repair of alkylation lesions in DNA, RNA, and nucleoprotein complexes. There are nine human and thirteen Arabidopsis thaliana ALKBH proteins described, which exhibit diversified functions. Among them, human ALKBH5 and FaT mass and Obesity-associated (FTO) protein and Arabidopsis ALKBH9B and ALKBH10B have been recognized as N6 methyladenine (N6 meA) demethylases, the most abundant posttranscriptional modification in mRNA. The FTO protein is reported to be associated with obesity and type 2 diabetes, and involved in multiple other processes, while ALKBH5 is induced by hypoxia. Arabidopsis ALKBH9B is an N6 meA demethylase influencing plant susceptibility to viral infections via m6 A/A ratio control in viral RNA. ALKBH10B has been discovered to be a functional Arabidopsis homolog of FTO; thus, it is also an RNA N6 meA demethylase involved in plant flowering and several other regulatory processes including control of metabolism. High-throughput mass spectrometry showed multiple sites of human ALKBH phosphorylation. In the case of FTO, the type of modified residue decides about the further processing of the protein. This modification may result in subsequent protein ubiquitination and proteolysis, or in the blocking of these processes. However, the impact of phosphorylation on the other ALKBH function and their downstream pathways remains nearly unexplored in both human and Arabidopsis. Therefore, the investigation of evolutionarily conserved functions of ALKBH proteins and their regulatory impact on important cellular processes is clearly called for. |
Databáze: | OpenAIRE |
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