Topic
AK2
About: AK2 is a research topic. Over the lifetime, 46 publications have been published within this topic receiving 1250 citations. The topic is also known as: ATP-AMP transphosphorylase 2 & adenylate kinase isoenzyme 2, mitochondrial.
Papers
Centre national de la recherche scientifique1, French Institute of Health and Medical Research2, Paris Descartes University3, University of Paris4, National Institutes of Health5, Baylor College of Medicine6, French Alternative Energies and Atomic Energy Commission7, Boston Children's Hospital8, Collège de France9, Necker-Enfants Malades Hospital10
TL;DR: It is demonstrated that restoration of AK2 expression in the bone marrow cells of individuals with reticular dysgenesis overcomes the neutrophil differentiation arrest, underlining its specific requirement in the development of a restricted set of hematopoietic lineages.
Abstract: Reticular dysgenesis is an autosomal recessive form of human severe combined immunodeficiency characterized by an early differentiation arrest in the myeloid lineage and impaired lymphoid maturation. In addition, affected newborns have bilateral sensorineural deafness. Here we identify biallelic mutations in AK2 (adenylate kinase 2) in seven individuals affected with reticular dysgenesis. These mutations result in absent or strongly decreased protein expression. We then demonstrate that restoration of AK2 expression in the bone marrow cells of individuals with reticular dysgenesis overcomes the neutrophil differentiation arrest, underlining its specific requirement in the development of a restricted set of hematopoietic lineages. Last, we establish that AK2 is specifically expressed in the stria vascularis region of the inner ear, which provides an explanation of the sensorineural deafness in these individuals. These results identify a previously unknown mechanism involved in regulation of hematopoietic cell differentiation and in one of the most severe human immunodeficiency syndromes.
226 citations
TL;DR: It is demonstrated that a physiologically relevant concentration of tBid is sufficient to induce release of particular intermembrane mitochondrial proteins belonging to a broad molecular-mass range.
Abstract: A crucial event in the process of apoptosis is caspase-dependent generation of truncated Bid (tBid), inducing release of cytochrome c. In an in vitro reconstitution system we combined purified recombinant tBid with isolated liver mitochondria and identified the released proteins using a proteomic matrix-assisted laser desorption ionization post-source decay (MALDI-PSD) approach. In order to meet physiological conditions, the concentration of tBid was chosen such that it was unable to induce cytochrome c release in mitochondria derived from liver-specific Bcl-2-transgenic mice. Several mitochondrial proteins were identified to be released in a tBid-dependent way, among which cytochrome c, DIABLO/Smac, adenylate kinase 2, acyl-CoA-binding protein, endonuclease G, polypyrimidine tract-binding protein, a type-I RNA helicase, a WD-40 repeat-containing protein and the serine protease Omi. Western blotting confirmed the absence of adenylate kinase 3, a matrix mitochondrial protein. These results demonstrate that a physiologically relevant concentration of tBid is sufficient to induce release of particular intermembrane mitochondrial proteins belonging to a broad molecular-mass range.
84 citations
TL;DR: It is demonstrated that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages, showing thatAK2 is critical in the control of energy metabolism.
Abstract: Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular - showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation.
79 citations
TL;DR: The results suggest that AK2 is an associated activator of DUSP26 and suppresses cell proliferation by FADD dephosphorylation, postulating AK2 as a negative regulator of tumour growth.
Abstract: Adenylate kinase 2 can bind to FADD. In this study, Kim et al. show that adenylate kinase 2 is a tumour suppressor and interacts with the phosphatase DUSP6, and this in turn regulates the phosphorylation of FADD.
63 citations
TL;DR: The finding that adenylate kinase 2 (AK2), a mitochondrial enzyme that regulates adenine nucleotide interconversion within the intermembrane space, is markedly induced during adipocyte and B cell differentiation is revealed and suggests that specific mitochondrial defects may give rise to impaired UPR signaling.
61 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 2 |
| 2020 | 2 |
| 2019 | 1 |
| 2018 | 3 |
| 2016 | 1 |
| 2015 | 3 |