| 1. |
- Caballero, Antonio, et al.
(författare)
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Absence of mitochondrial translation control proteins extends life span by activating sirtuin-dependent silencing.
- 2011
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Ingår i: Molecular cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 42:3, s. 390-400
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Tidskriftsartikel (refereegranskat)abstract
- Altered mitochondrial functionality can extend organism life span, but the underlying mechanisms are obscure. Here we report that inactivating SOV1, a member of the yeast mitochondrial translation control (MTC) module, causes a robust Sir2-dependent extension of replicative life span in the absence of respiration and without affecting oxidative damage. We found that SOV1 interacts genetically with the cAMP-PKA pathway and the chromatin remodeling apparatus. Consistently, Sov1p-deficient cells displayed reduced cAMP-PKA signaling and an elevated, Sir2p-dependent, genomic silencing. Both increased silencing and life span extension in sov1Δ cells require the PKA/Msn2/4p target Pnc1p, which scavenges nicotinamide, a Sir2p inhibitor. Inactivating other members of the MTC module also resulted in Sir2p-dependent life span extension. The data demonstrate that the nuclear silencing apparatus senses and responds to the absence of MTC proteins and that this response converges with a pathway for life span extension elicited by reducing TOR signaling.
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| 2. |
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| 3. |
- Nachin, Laurence, 1971, et al.
(författare)
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Differential roles of the universal stress proteins of Escherichia coli in oxidative stress resistance, adhesion, and motility
- 2005
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Ingår i: Journal of Bacteriology. - 0021-9193. ; 187:18, s. 6265-6272
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Tidskriftsartikel (refereegranskat)abstract
- The universal stress protein (UspA) superfamily encompasses a conserved group of proteins that are found in bacteria, archaea, and eukaryotes. Escherichia coli harbors six usp genesuspA, -C, -D, -E, -F, and -Gthe expression of which is triggered by a large variety of environmental insults. The uspA gene is important for survival during cellular growth arrest, but the exact physiological role of the Usp proteins is not known. In this work we have performed phenotypic characterization of mutants with deletions of the six different usp genes. We report on hitherto unknown functions of these genes linked to motility, adhesion, and oxidative stress resistance, and we show that usp functions are both overlapping and distinct. Both UspA and UspD are required in the defense against superoxide-generating agents, and UspD appears also important in controlling intracellular levels of iron. In contrast, UspC is not involved in stress resistance or iron metabolism but is essential, like UspE, for cellular motility. Electron microscopy demonstrates that uspC and uspE mutants are devoid of flagella. In addition, the function of the uspC and uspE genes is linked to cell adhesion, measured as FimH-mediated agglutination of yeast cells. While the UspC and UspE proteins promote motility at the expense of adhesion, the UspF and UspG proteins exhibit the exact opposite effects. We suggest that the Usp proteins have evolved different physiological functions that reprogram the cell towards defense and escape during cellular stress
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| 4. |
- Nachin, Laurence, 1971, et al.
(författare)
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Heterodimer formation within universal stress protein classes revealed by an in silico and experimental approach.
- 2008
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Ingår i: Journal of molecular biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 380:2, s. 340-50
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Tidskriftsartikel (refereegranskat)abstract
- Universal stress proteins (Usps) are found in all kingdoms of life and can be divided into four classes by phylogenic analysis. According to available structures, Usps exist as homodimers, and genetic studies show that their cellular assignments are extensive, including functions relating to stress resistance, carbon metabolism, cellular adhesion, motility, and bacterial virulence. We approached the question of how Usps can achieve such a variety of functions in a cell by using a new procedure for statistical analysis of multiple sequence alignments, based on physicochemically related values for each amino acid residue of Usp dimer interfaces. The results predicted that Usp proteins within a class may, in addition to forming homodimers, be able to form heterodimers. Using Escherichia coli Usps as model proteins, we confirmed the existence of such interactions. We especially focused on class I UspA and UspC and demonstrated that they are able to form homo- and heterodimers in vitro and in vivo. We suggest that this ability to form both homo- and heterodimers may allow for an expansion of the functional repertoire of Usps and explains why organisms usually contain multiple usp paralogues.
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