Genomes and Genes
Gene Symbol: skn-1
Description: Protein skinhead-1;SKiNhead
Alias: Protein skinhead-1;SKiNhead
Species: Caenorhabditis elegans
- Maduro M, Broitman Maduro G, Mengarelli I, Rothman J. Maternal deployment of the embryonic SKN-1-->MED-1,2 cell specification pathway in C. elegans. Dev Biol. 2007;301:590-601 pubmed
- Hoeven R, McCallum K, Cruz M, Garsin D. Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1 activity via p38 MAPK signaling during infection in C. elegans. PLoS Pathog. 2011;7:e1002453 pubmed publisher..Overall, a model is presented in which ROS generation by Ce-Duox1/BLI-3 activates a protective SKN-1 response via p38 MAPK signaling. ..
- Przybysz A, Choe K, Roberts L, Strange K. Increased age reduces DAF-16 and SKN-1 signaling and the hormetic response of Caenorhabditis elegans to the xenobiotic juglone. Mech Ageing Dev. 2009;130:357-69 pubmed publisher..Our studies provide a foundation for developing a molecular understanding of how age affects cytoprotective transcriptional pathways. ..
- Staab T, Evgrafov O, Egrafov O, Knowles J, Sieburth D. Regulation of synaptic nlg-1/neuroligin abundance by the skn-1/Nrf stress response pathway protects against oxidative stress. PLoS Genet. 2014;10:e1004100 pubmed publisher..Together, our results suggest that SKN-1 activation in the nervous system can confer protection to organisms in response to stress by directly regulating nlg-1/neuroligin expression. ..
- Paek J, Lo J, Narasimhan S, Nguyen T, Glover Cutter K, Robida Stubbs S, et al. Mitochondrial SKN-1/Nrf mediates a conserved starvation response. Cell Metab. 2012;16:526-37 pubmed publisher..Our findings delineate an evolutionarily conserved metabolic axis of SKN-1/Nrf, further establishing the complexity of this pathway. ..
- Kawli T, Wu C, Tan M. Systemic and cell intrinsic roles of Gqalpha signaling in the regulation of innate immunity, oxidative stress, and longevity in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2010;107:13788-93 pubmed publisher..We propose a model whereby Gqalpha signaling differentially regulates pathogen sensitivity, oxidative stress, and longevity through cell autonomous and noncell autonomous effects on p38 MAPK and insulin/IGF1 signaling, respectively. ..
- Kell A, Ventura N, Kahn N, Johnson T. Activation of SKN-1 by novel kinases in Caenorhabditis elegans. Free Radic Biol Med. 2007;43:1560-6 pubmed..Inhibition of two of these kinases results in shorter life span and increased sensitivity to stress. ..
- Park S, Tedesco P, Johnson T. Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1. Aging Cell. 2009;8:258-69 pubmed publisher..These findings showed that a transcriptional shift from growth and maintenance towards the activation of cellular defense mechanisms was caused by the oxidative stress; many of these transcriptional alterations are SKN-1 dependent. ..
- Maduro M, Hill R, Heid P, Newman Smith E, Zhu J, Priess J, et al. Genetic redundancy in endoderm specification within the genus Caenorhabditis. Dev Biol. 2005;284:509-22 pubmed..briggsae end genes also function redundantly to specify endoderm. We propose that duplicated end genes have been maintained over long periods of evolution, owing in part to their synergistic function. ..
- An J, Vranas K, Lucke M, Inoue H, Hisamoto N, Matsumoto K, et al. Regulation of the Caenorhabditis elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-3. Proc Natl Acad Sci U S A. 2005;102:16275-80 pubmed..We conclude that (i) GSK-3 inhibits SKN-1 activity in the intestine, (ii) the phase II response integrates multiple regulatory signals, and (iii), by inhibiting this response, GSK-3 may influence redox conditions. ..
- Glover Cutter K, Lin S, Blackwell T. Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. PLoS Genet. 2013;9:e1003701 pubmed publisher..Regulatory integration through SKN-1/Nrf may coordinate ER and cytoplasmic homeostasis. ..
- Park S, Link C, Johnson T. Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J. 2010;24:383-92 pubmed publisher..We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans. ..
- Staab T, Griffen T, Corcoran C, Evgrafov O, Knowles J, Sieburth D. The conserved SKN-1/Nrf2 stress response pathway regulates synaptic function in Caenorhabditis elegans. PLoS Genet. 2013;9:e1003354 pubmed publisher..These results provide insight into how SKN-1/Nrf2 might protect the nervous system from damage in response to oxidative stress. ..
- Tullet J, Hertweck M, An J, Baker J, Hwang J, Liu S, et al. Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell. 2008;132:1025-38 pubmed publisher..Furthermore, SKN-1 that is constitutively active increases life span independently of DAF-16. Our findings indicate that the transcription network regulated by SKN-1 promotes longevity and is an important direct target of IIS. ..
- Lin R, Thompson S, Priess J. pop-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos. Cell. 1995;83:599-609 pubmed..We propose that POP-1 and SKN-1 function together in the early embryo to allow MS-specific differentiation. ..
- Bowerman B, Draper B, Mello C, Priess J. The maternal gene skn-1 encodes a protein that is distributed unequally in early C. elegans embryos. Cell. 1993;74:443-52 pubmed
- Inoue H, Hisamoto N, An J, Oliveira R, Nishida E, Blackwell T, et al. The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev. 2005;19:2278-83 pubmed..These results delineate the C. elegans p38 MAPK signaling pathway leading to the nucleus that responds to oxidative stress. ..
- Bowerman B, Eaton B, Priess J. skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. elegans embryo. Cell. 1992;68:1061-75 pubmed..We propose that the maternally expressed skn-1 gene product acts to specify the fate of the EMS blastomere. ..
- An J, Blackwell T. SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev. 2003;17:1882-93 pubmed..This oxidative stress response thus appears to be both widely conserved and ancient, suggesting that the mesendodermal specification role of SKN-1 was predated by its function in these detoxification mechanisms. ..
- Raj A, Rifkin S, Andersen E, van Oudenaarden A. Variability in gene expression underlies incomplete penetrance. Nature. 2010;463:913-8 pubmed publisher..Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation. ..
- Hunt P, Son T, Wilson M, Yu Q, Wood W, Zhang Y, et al. Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms. PLoS ONE. 2011;6:e21922 pubmed publisher..Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway. ..
- Ogawa T, Kodera Y, Hirata D, Blackwell T, Mizunuma M. Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf. Sci Rep. 2016;6:21611 pubmed publisher..Our data also indicate that thioallyl structure and the number of sulfur atoms are important for SKN-1 target induction. Our results indicate that SAC and SAMC may serve as potential agents that slow aging. ..
- Wu C, Deonarine A, Przybysz A, Strange K, Choe K. The Skp1 Homologs SKR-1/2 Are Required for the Caenorhabditis elegans SKN-1 Antioxidant/Detoxification Response Independently of p38 MAPK. PLoS Genet. 2016;12:e1006361 pubmed publisher..Together, these results identify a novel p38 MAPK independent signaling mechanism that activates SKN-1 via SKR-1/2 and involves WDR-23. ..
- Rizki G, Picard C, Pereyra C, Lee S. Host cell factor 1 inhibits SKN-1 to modulate oxidative stress responses in Caenorhabditis elegans. Aging Cell. 2012;11:717-21 pubmed publisher..Our findings reveal a novel and context-specific regulatory relationship between two highly conserved longevity and stress response factors HCF-1 and SKN-1...
- Robertson S, Shetty P, Lin R. Identification of lineage-specific zygotic transcripts in early Caenorhabditis elegans embryos. Dev Biol. 2004;276:493-507 pubmed..These results demonstrate the successful combination of single-staged embryo cDNAs, genetic mutants, and whole transcriptome microarray analysis to identify stage- and lineage-specific transcripts in early C. elegans embryos. ..
- GHOSE P, Park E, Tabakin A, Salazar Vasquez N, Rongo C. Anoxia-reoxygenation regulates mitochondrial dynamics through the hypoxia response pathway, SKN-1/Nrf, and stomatin-like protein STL-1/SLP-2. PLoS Genet. 2013;9:e1004063 pubmed publisher..Our results suggest the existence of a conserved anoxic stress response involving changes in mitochondrial fission and fusion. ..
- Pang S, Lynn D, Lo J, Paek J, Curran S. SKN-1 and Nrf2 couples proline catabolism with lipid metabolism during nutrient deprivation. Nat Commun. 2014;5:5048 pubmed publisher..Our findings identify a link between proline catabolism and lipid metabolism, and uncover a physiological role for SKN-1 in metabolism. ..
- Wang Z, Ma X, Li J, Cui X. Peptides from sesame cake extend healthspan of Caenorhabditis elegans via upregulation of skn-1 and inhibition of intracellular ROS levels. Exp Gerontol. 2016;82:139-49 pubmed publisher..Current results warrant research into the use of PSC as nutraceuticals for overall health improvement. ..
- Wu C, Wang Y, Choe K. F-Box Protein XREP-4 Is a New Regulator of the Oxidative Stress Response in Caenorhabditis elegans. Genetics. 2017;206:859-871 pubmed publisher..These results are consistent with XREP-4 influencing the SKN-1 stress response by functioning as a bridge between WDR-23 and the ubiquitin ligase component SKR-1. ..
- Steinbaugh M, Narasimhan S, Robida Stubbs S, Moronetti Mazzeo L, Dreyfuss J, Hourihan J, et al. Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence. elife. 2015;4: pubmed publisher..This SKN-1 function may explain the importance of mammalian Nrf proteins in fatty liver disease and suggest that particular endogenous or dietary lipids might promote health through SKN-1/Nrf. ..
- Blackwell T, Steinbaugh M, Hourihan J, Ewald C, Isik M. SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. Free Radic Biol Med. 2015;88:290-301 pubmed publisher..elegans studies predict that mammalian Nrf/CNC protein functions and regulation may be similarly complex and that the proteins and processes that they regulate are likely to have a major influence on mammalian life- and healthspan. ..
- Hibshman J, Hung A, Baugh L. Maternal Diet and Insulin-Like Signaling Control Intergenerational Plasticity of Progeny Size and Starvation Resistance. PLoS Genet. 2016;12:e1006396 pubmed publisher..This work reveals maternal provisioning as an organismal response to DR, demonstrates potentially adaptive intergenerational phenotypic plasticity, and identifies conserved pathways mediating these effects. ..
- Chew Y, GÃ¶tz J, Nicholas H. Neuronal protein with tau-like repeats (PTL-1) regulates intestinal SKN-1 nuclear accumulation in response to oxidative stress. Aging Cell. 2015;14:148-51 pubmed publisher..Our data also suggest that PTL-1 functions via neurons to modulate SKN-1, clarifying the role of this protein in the stress response and longevity. ..
- Mendes T, Novakovic S, Raymant G, Bertram S, Esmaillie R, Nadarajan S, et al. Investigating the role of RIO protein kinases in Caenorhabditis elegans. PLoS ONE. 2015;10:e0117444 pubmed publisher..Taken together, our findings indicate new functions for RIOK-1 in post mitotic tissues and in reproduction. ..
- Wu J, Huang J, Khanabdali R, Kalionis B, Xia S, Cai W. Pyrroloquinoline quinone enhances the resistance to oxidative stress and extends lifespan upon DAF-16 and SKN-1 activities in C. elegans. Exp Gerontol. 2016;80:43-50 pubmed publisher..2, gst-1 and gst-10. Our findings uncover a novel role of PQQ in longevity, supporting PQQ as a possible dietary supplement for overall health improvement. ..
- Schreiber M, Pierce Shimomura J, Chan S, Parry D, McIntire S. Manipulation of behavioral decline in Caenorhabditis elegans with the Rag GTPase raga-1. PLoS Genet. 2010;6:e1000972 pubmed publisher..This work indicates that novel modulators of behavioral function can be identified in screens, with implications for future study of the clinical amelioration of age-related decline. ..
- Leiser S, Fletcher M, Begun A, Kaeberlein M. Life-span extension from hypoxia in Caenorhabditis elegans requires both HIF-1 and DAF-16 and is antagonized by SKN-1. J Gerontol A Biol Sci Med Sci. 2013;68:1135-44 pubmed publisher..Collectively, our results show that hypoxia modulates longevity in a complex manner, likely involving components in addition to HIF-1. ..
- Carroll A, Gilbert D, Liu X, Cheung J, Michnowicz J, Wagner G, et al. SKN-1 domain folding and basic region monomer stabilization upon DNA binding. Genes Dev. 1997;11:2227-38 pubmed..This is similar to how the bZIP basic region extends from the leucine zipper, indicating that positioning and cooperative stability provided by helix extension are conserved mechanisms that promote binding of basic regions to DNA. ..
- Tang H, Pang S. Proline Catabolism Modulates Innate Immunity in Caenorhabditis elegans. Cell Rep. 2016;17:2837-2844 pubmed publisher..Our findings reveal how animals utilize metabolism of a single amino acid to defend against a pathogen and identify proline catabolism as a component of innate immune signaling. ..
- Rupert P, Daughdrill G, Bowerman B, Matthews B. A new DNA-binding motif in the Skn-1 binding domain-DNA complex. Nat Struct Biol. 1998;5:484-91 pubmed..Skn-1, however, lacks the leucine zipper found in all bZips. Additional contacts with the DNA are made by a short basic segment at the N-terminus of the domain, reminiscent of the 'homeodomain arm'. ..
- Havermann S, Humpf H, Watjen W. Baicalein modulates stress-resistance and life span in C. elegans via SKN-1 but not DAF-16. Fitoterapia. 2016;113:123-7 pubmed publisher..elegans via SKN-1 but not DAF-16. ..
- Lin R. A gain-of-function mutation in oma-1, a C. elegans gene required for oocyte maturation, results in delayed degradation of maternal proteins and embryonic lethality. Dev Biol. 2003;258:226-39 pubmed..These observations suggest that oma-1, in addition to its role in oocyte maturation, contributes to early embryonic development by regulating the temporal degradation of maternal proteins in early C. elegans embryos. ..
- Huang S, Shetty P, Robertson S, Lin R. Binary cell fate specification during C. elegans embryogenesis driven by reiterated reciprocal asymmetry of TCF POP-1 and its coactivator beta-catenin SYS-1. Development. 2007;134:2685-95 pubmed..We propose that two genetic pathways, one increasing SYS-1 and the other decreasing POP-1 levels, robustly elevate the SYS-1-to-POP-1 ratio in the posterior cell, thereby driving A-P differential cell fates. ..
- Vora S, Phillips B. Centrosome-Associated Degradation Limits Î²-Catenin Inheritance by Daughter Cells after Asymmetric Division. Curr Biol. 2015;25:1005-16 pubmed publisher..Based on our observations of centrosomal SYS-1 dynamics, we discuss the possibility that the centrosome may coordinate various cell-cycle-dependent processes by synchronizing mitosis and protein regulation. ..
- Hunter C, Kenyon C. Spatial and temporal controls target pal-1 blastomere-specification activity to a single blastomere lineage in C. elegans embryos. Cell. 1996;87:217-26 pubmed
- Keith S, Maddux S, Zhong Y, Chinchankar M, Ferguson A, Ghazi A, et al. Graded Proteasome Dysfunction in Caenorhabditis elegans Activates an Adaptive Response Involving the Conserved SKN-1 and ELT-2 Transcription Factors and the Autophagy-Lysosome Pathway. PLoS Genet. 2016;12:e1005823 pubmed publisher
- Choe K, Leung C, Miyamoto M. Unique structure and regulation of the nematode detoxification gene regulator, SKN-1: implications to understanding and controlling drug resistance. Drug Metab Rev. 2012;44:209-23 pubmed publisher..Protein alignment and phylogenetic analyses indicate that these differences are shared among many nematodes, making SKN-1 a candidate for specifically targeting nematode detoxification and antioxidation...
- Hu Q, D Amora D, MacNeil L, Walhout A, Kubiseski T. The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2. Genetics. 2017;206:1909-1922 pubmed publisher..elegans. ..
- Ferguson A, Springer M, Fisher A. skn-1-Dependent and -independent regulation of aip-1 expression following metabolic stress in Caenorhabditis elegans. Mol Cell Biol. 2010;30:2651-67 pubmed publisher..These may be triggered by proteosome dysfunction, as we find that this event links the multiple inducers of aip-1. Together, our results show that cell stress triggers aip-1 expression by both skn-1-dependent and -independent pathways. ..
- Ruf V, Holzem C, Peyman T, Walz G, Blackwell T, Neumann Haefelin E. TORC2 signaling antagonizes SKN-1 to induce C. elegans mesendodermal embryonic development. Dev Biol. 2013;384:214-27 pubmed publisher..The SGK-1 kinase mediated these functions downstream of rict-1/TORC2, as a sgk-1 gain-of-function mutant suppressed the rict-1 mutant phenotype. These data indicate that TORC2 and SGK-1 antagonize SKN-1 during embryonic development...
- Smith Vikos T, de Lencastre A, Inukai S, Shlomchik M, Holtrup B, Slack F. MicroRNAs mediate dietary-restriction-induced longevity through PHA-4/FOXA and SKN-1/Nrf transcription factors. Curr Biol. 2014;24:2238-46 pubmed publisher..elegans. Given the conservation of miRNAs, PHA-4, and SKN-1 across phylogeny, these interactions are likely to be conserved in more-complex species. ..
- Mouchiroud L, Molin L, Kasturi P, Triba M, Dumas M, Wilson M, et al. Pyruvate imbalance mediates metabolic reprogramming and mimics lifespan extension by dietary restriction in Caenorhabditis elegans. Aging Cell. 2011;10:39-54 pubmed publisher..These findings suggest that inhibition of this transporter homolog in mammals might also promote a DR response. ..
- Lin K, Broitman Maduro G, Hung W, Cervantes S, Maduro M. Knockdown of SKN-1 and the Wnt effector TCF/POP-1 reveals differences in endomesoderm specification in C. briggsae as compared with C. elegans. Dev Biol. 2009;325:296-306 pubmed publisher..Our results suggest that integration of Wnt-dependent and Wnt-independent cell fate specification pathways within the Caenorhabditis genus can occur in different ways. ..
- Dostal V, Roberts C, Link C. Genetic mechanisms of coffee extract protection in a Caenorhabditis elegans model of ?-amyloid peptide toxicity. Genetics. 2010;186:857-66 pubmed publisher..These results suggest that the reported protective effects of coffee in multiple neurodegenerative diseases may result from a general activation of the Nrf2 phase II detoxification pathway. ..
- Page B, Diede S, Tenlen J, Ferguson E. EEL-1, a Hect E3 ubiquitin ligase, controls asymmetry and persistence of the SKN-1 transcription factor in the early C. elegans embryo. Development. 2007;134:2303-14 pubmed..These data strongly suggest that multiple, functionally redundant pathways cooperate to ensure precise control of SKN-1 asymmetry and persistence in the early embryo. ..