Specific SKN-1/Nrf Stress Responses to Perturbations in Translation Elongation and Proteasome Activity
SKN-1, the Caenorhabditis elegans Nrf1/2/3 ortholog, promotes both oxidative stress resistance and longevity. SKN-1 responds to oxidative stress by upregulating genes that detoxify and defend against free radicals and other reactive molecules, a SKN-1/Nrf function that is both well-known and conserved. Here we show that SKN-1 has a broader and more complex role in maintaining cellular stress defenses. SKN-1 sustains expression and activity of the ubiquitin-proteasome system (UPS) and coordinates specific protective responses to perturbations in protein synthesis or degradation through the UPS. If translation initiation or elongation is impaired, SKN-1 upregulates overlapping sets of cytoprotective genes and increases stress resistance. When proteasome gene expression and activity are blocked, SKN-1 activates multiple classes of proteasome subunit genes in a compensatory response. SKN-1 thereby maintains UPS activity in the intestine in vivo under normal conditions and promotes survival when the proteasome is inhibited. In contrast, when translation elongation is impaired, SKN-1 does not upregulate proteasome genes, and UPS activity is then reduced. This indicates that UPS activity depends upon presence of an intact translation elongation apparatus; and it supports a model, suggested by genetic and biochemical studies in yeast, that protein synthesis and degradation may be coupled processes. SKN-1 therefore has a critical tissue-specific function in increasing proteasome gene expression and UPS activity under normal conditions, as well as when the UPS system is stressed, but mounts distinct responses when protein synthesis is perturbed. The specificity of these SKN-1–mediated stress responses, along with the apparent coordination between UPS and translation elongation activity, may promote protein homeostasis under stress or disease conditions. The data suggest that SKN-1 may increase longevity, not only through its well-documented role in boosting stress resistance, but also through contributing to protein homeostasis.
Vyšlo v časopise:
Specific SKN-1/Nrf Stress Responses to Perturbations in Translation Elongation and Proteasome Activity. PLoS Genet 7(6): e32767. doi:10.1371/journal.pgen.1002119
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002119
Souhrn
SKN-1, the Caenorhabditis elegans Nrf1/2/3 ortholog, promotes both oxidative stress resistance and longevity. SKN-1 responds to oxidative stress by upregulating genes that detoxify and defend against free radicals and other reactive molecules, a SKN-1/Nrf function that is both well-known and conserved. Here we show that SKN-1 has a broader and more complex role in maintaining cellular stress defenses. SKN-1 sustains expression and activity of the ubiquitin-proteasome system (UPS) and coordinates specific protective responses to perturbations in protein synthesis or degradation through the UPS. If translation initiation or elongation is impaired, SKN-1 upregulates overlapping sets of cytoprotective genes and increases stress resistance. When proteasome gene expression and activity are blocked, SKN-1 activates multiple classes of proteasome subunit genes in a compensatory response. SKN-1 thereby maintains UPS activity in the intestine in vivo under normal conditions and promotes survival when the proteasome is inhibited. In contrast, when translation elongation is impaired, SKN-1 does not upregulate proteasome genes, and UPS activity is then reduced. This indicates that UPS activity depends upon presence of an intact translation elongation apparatus; and it supports a model, suggested by genetic and biochemical studies in yeast, that protein synthesis and degradation may be coupled processes. SKN-1 therefore has a critical tissue-specific function in increasing proteasome gene expression and UPS activity under normal conditions, as well as when the UPS system is stressed, but mounts distinct responses when protein synthesis is perturbed. The specificity of these SKN-1–mediated stress responses, along with the apparent coordination between UPS and translation elongation activity, may promote protein homeostasis under stress or disease conditions. The data suggest that SKN-1 may increase longevity, not only through its well-documented role in boosting stress resistance, but also through contributing to protein homeostasis.
Zdroje
1. GoldbergAL 2003 Protein degradation and protection against misfolded or damaged proteins. Nature 426 895 899
2. MorimotoRICuervoAM 2009 Protein homeostasis and aging: taking care of proteins from the cradle to the grave. J Gerontol A Biol Sci Med Sci 64 167 170
3. BalchWEMorimotoRIDillinAKellyJW 2008 Adapting proteostasis for disease intervention. Science 319 916 919
4. Bousquet-DubouchMPNguenSBouyssieDBurlet-SchiltzOFrenchSW 2009 Chronic ethanol feeding affects proteasome-interacting proteins. Proteomics 9 3609 3622
5. CiechanoverA 2005 Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6 79 87
6. GuerreroCMilenkovicTPrzuljNKaiserPHuangL 2008 Characterization of the proteasome interaction network using a QTAX-based tag-team strategy and protein interaction network analysis. Proc Natl Acad Sci U S A 105 13333 13338
7. VermaRChenSFeldmanRSchieltzDYatesJ 2000 Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol Biol Cell 11 3425 3439
8. BrowneGJProudCG 2002 Regulation of peptide-chain elongation in mammalian cells. Eur J Biochem 269 5360 5368
9. ChuangSMChenLLambertsonDAnandMKinzyTG 2005 Proteasome-mediated degradation of cotranslationally damaged proteins involves translation elongation factor 1A. Mol Cell Biol 25 403 413
10. GonenHSmithCESiegelNRKahanaCMerrickWC 1994 Protein synthesis elongation factor EF-1 alpha is essential for ubiquitin-dependent degradation of certain N alpha-acetylated proteins and may be substituted for by the bacterial elongation factor EF-Tu. Proc Natl Acad Sci U S A 91 7648 7652
11. DavyABelloPThierry-MiegNVaglioPHittiJ 2001 A protein-protein interaction map of the Caenorhabditis elegans 26S proteasome. EMBO Rep 2 821 828
12. SchubertUAntonLCGibbsJNorburyCCYewdellJW 2000 Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404 770 774
13. TurnerGCVarshavskyA 2000 Detecting and measuring cotranslational protein degradation in vivo. Science 289 2117 2120
14. ShaZBrillLMCabreraRKleifeldOScheligaJS 2009 The eIF3 interactome reveals the translasome, a supercomplex linking protein synthesis and degradation machineries. Mol Cell 36 141 152
15. SykiotisGPBohmannD 2010 Stress-activated cap‘n’collar transcription factors in aging and human disease. Sci Signal 3 re3
16. ArltABauerISchafmayerCTepelJMuerkosterSS 2009 Increased proteasome subunit protein expression and proteasome activity in colon cancer relate to an enhanced activation of nuclear factor E2-related factor 2 (Nrf2). Oncogene 28 3983 3996
17. KraftDCDeocarisCCWadhwaRRattanSI 2006 Preincubation with the proteasome inhibitor MG-132 enhances proteasome activity via the Nrf2 transcription factor in aging human skin fibroblasts. Ann N Y Acad Sci 1067 420 424
18. RadhakrishnanSKLeeCSYoungPBeskowAChanJY 2010 Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Mol Cell 38 17 28
19. SteffenJSeegerMKochAKrugerE 2010 Proteasomal degradation is transcriptionally controlled by TCF11 via an ERAD-dependent feedback loop. Mol Cell 40 147 158
20. OliveiraRPPorter AbateJDilksKLandisJAshrafJ 2009 Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging Cell 8 524 541
21. ParkSKTedescoPMJohnsonTE 2009 Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1. Aging Cell 8 258 269
22. NiuWLuZJZhongMSarovMMurrayJI 2011 Diverse transcription factor binding features revealed by genome-wide ChIP-seq in C. elegans. Genome Res 21 245 254
23. WangJRobida-StubbsSTulletJMRualJFVidalM 2010 RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition. PLoS Genet 6 e1001048 doi:10.1371/journal.pgen.1001048
24. AnJHBlackwellTK 2003 SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17 1882 1893
25. TulletJMHertweckMAnJHBakerJHwangJY 2008 Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132 1025 1038
26. KahnNWReaSLMoyleSKellAJohnsonTE 2008 Proteasomal dysfunction activates the transcription factor SKN-1 and produces a selective oxidative-stress response in Caenorhabditis elegans. Biochem J 409 205 213
27. ChoeKPPrzybyszAJStrangeK 2009 The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans. Mol Cell Biol 29 2704 2715
28. Schneider-PoetschTJuJEylerDEDangYBhatS 2010 Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat Chem Biol 6 209 217
29. InoueHHisamotoNAnJHOliveiraRPNishidaE 2005 The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev 19 2278 2283
30. KimDHFeinbaumRAlloingGEmersonFEGarsinDA 2002 A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297 623 626
31. CalfonMZengHUranoFTillJHHubbardSR 2002 IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415 92 96
32. HaynesCMYangYBlaisSPNeubertTARonD 2010 The matrix peptide exporter HAF-1 signals a mitochondrial UPR by activating the transcription factor ZC376.7 in C. elegans. Mol Cell 37 529 540
33. MorleyJFMorimotoRI 2004 Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15 657 664
34. PanKZPalterJERogersANOlsenAChenD 2007 Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 6 111 119
35. HansenMTaubertSCrawfordDLibinaNLeeSJ 2007 Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6 95 110
36. TohyamaDYamaguchiAYamashitaT 2008 Inhibition of a eukaryotic initiation factor (eIF2Bdelta/F11A3.2) during adulthood extends lifespan in Caenorhabditis elegans. FASEB J 22 4327 4337
37. LinKHsinHLibinaNKenyonC 2001 Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28 139 145
38. YamawakiTMArantes-OliveiraNBermanJRZhangPKenyonC 2008 Distinct activities of the germline and somatic reproductive tissues in the regulation of Caenorhabditis elegans' longevity. Genetics 178 513 526
39. Halaschek-WienerJKhattraJSMcKaySPouzyrevAStottJM 2005 Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression. Genome Res 15 603 615
40. HamerGMatilainenOHolmbergCI 2010 A photoconvertible reporter of the ubiquitin-proteasome system in vivo. Nat Methods 7 473 478
41. DantumaNPLindstenKGlasRJellneMMasucciMG 2000 Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells. Nat Biotechnol 18 538 543
42. NollenEAGarciaSMvan HaaftenGKimSChavezA 2004 Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation. Proc Natl Acad Sci U S A 101 6403 6408
43. SonenbergNHinnebuschAG 2009 Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136 731 745
44. LohKDengHFukushimaACaiXBoivinB 2009 Reactive oxygen species enhance insulin sensitivity. Cell Metab 10 260 272
45. XuZChenLLeungLYenTSLeeC 2005 Liver-specific inactivation of the Nrf1 gene in adult mouse leads to nonalcoholic steatohepatitis and hepatic neoplasia. Proc Natl Acad Sci U S A 102 4120 4125
46. AlavezSVantipalliMCZuckerDJSKlangIMLithgowGJ 2011 Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature
47. RualJFCeronJKorethJHaoTNicotAS 2004 Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res 14 2162 2168
48. Glover-CutterKKimSEspinosaJBentleyDL 2008 RNA polymerase II pauses and associates with pre-mRNA processing factors at both ends of genes. Nat Struct Mol Biol 15 71 78
49. ProudCG 1994 Peptide-chain elongation in eukaryotes. Mol Biol Rep 19 161 170
50. PrahladVCorneliusTMorimotoRI 2008 Regulation of the cellular heat shock response in Caenorhabditis elegans by thermosensory neurons. Science 320 811 814
51. LinkCDCypserJRJohnsonCJJohnsonTE 1999 Direct observation of stress response in Caenorhabditis elegans using a reporter transgene. Cell Stress Chaperones 4 235 242
52. PispaJPalmenSHolmbergCIJanttiJ 2008 C. elegans dss-1 is functionally conserved and required for oogenesis and larval growth. BMC Dev Biol 8 51
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 6
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