1. Feeling Spunky With JNK -- Davenport 2005 (13): nf24 -- <i>Science</i>'s SAGE KE
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Novartis Inst. for Biomedical Research
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Sci. Aging Knowl. Environ., 30 March 2005
Vol. 2005, Issue 13, p. nf24
[DOI: 10.1126/sageke.2005.13.nf24]
NEWS FOCUS
Feeling Spunky With JNK
Protein funnels stress signals into insulin pathway and extends life
R. John Davenport
http://sageke.sciencemag.org/cgi/content/full/2005/13/nf24
Only a masochist would choose a life of stress and starvation, yet organisms can last unusually long if they exploit
molecular pathways that respond to these pressures. Now, scientists reveal how one molecule connects two such
pathways and lengthens the lives of worms and flies. The protein is linked to diabetes in mammals, suggesting
that what benefits invertebrates might not be good for humans. Researchers need to probe deeper to understand
how it shapes mammalian longevity, experts say.
When nutrients are abundant, the insulin and insulin-like growth factor 1 signaling pathways in mammals spur
cells to absorb sugar and grow. During lean times, the pathways shut down, and cells enter survival mode.
Blocking an analogous pathway in flies and worms extends longevity. The long-lived animals are often better at
resisting stresses such as oxidizing chemicals. Two years ago, geneticist Heinrich Jasper of the University of
Rochester in New York and colleagues found that an extra shot of a protein called JNK fortifies flies against
oxidative stress and prolongs survival. Now, two teams of researchers have investigated how JNK influences
insulin-related signaling.
Geneticist Heidi Tissenbaum of the University of Massachusetts Medical School in Worcester and colleagues
investigated JNK's contribution to nematode life span. Upping JNK production extended worm life by 40%, they
found. Blunting insulin-related signaling switches on a gene-control protein called FOXO. The researchers
discovered that worms with extra JNK but no functioning FOXO did not live long, suggesting that the two proteins
collaborate. Similarly, flies with hyperactive JNK only live long if they tote a full dose of FOXO, Jasper's team
found in a separate study. Further experiments by Tissenbaum's team bolster the connection: FOXO clings to JNK
in cultured cells engineered to produce both proteins.
FOXO switches on when it receives a phosphate group, which pushes the protein into the cell's nucleus. Jasper's
team observed that sparking fly insulin-like signaling restrained FOXO in the cytoplasm. But upon activation of
JNK, cells trucked FOXO to the nucleus. Similarly, Tissenbaum and colleagues found that nuclei contained more
of the protein when worms also carried extra JNK. In addition, her group reported that JNK stitches a phosphate
onto FOXO in a test tube. Together, the results suggest that JNK delays aging by activating FOXO.
The direct connection between JNK and FOXO is surprising, says diabetes researcher Morris White of Harvard
University. Diabetes researchers have investigated the JNK-insulin link and found that JNK squelches insulin
signaling, but it does so by inactivating components of the pathway other than FOXO. However, there are some
hints that the new findings will hold true in mammals. In November 2004, cell-signaling researcher Boudewijn
Burgering of the University of Utrecht in the Netherlands and colleagues reported that when mammalian cells are
exposed to oxidants, JNK phosphorylates a FOXO protein. The two new papers "provide the genetic data for our
biochemical analysis," says Burgering, making "quite a compelling case" that the proteins work together. Whether
JNK promotes long life in mammals is unclear. Nixing JNK fends off diabetes, says White, but vigorous JNK might
protect certain tissues. For instance, the protein might render muscle or fat insensitive to insulin, but it might stifle
insulin production in the pancreas, which can damage the organ if left unchecked. Clarifying JNK's contribution to
human aging might reveal a stress-free way for us to ride to long life.
March 30, 2005
1. M. A. Essers et al., FOXO transcription factor activation by oxidative stress mediated by the small GTPase
Ral and JNK. EMBO J. 23, 4802-4812 (2004). doi:10.1038/sj.emboj.7600476 [CrossRef][Medline][UMlinks]
2. S. W. Oh et al., JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of
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![Feeling Spunky With JNK -- Davenport 2005 (13): nf24 -- <i>Science</i>'s SAGE KE
http://sageke.sciencemag.org.ezproxy.umassmed.edu/cgi/content/full/2005/13/nf24[4/11/2011 12:14:17 PM]
Novartis Inst. for Biomedical Research
Home > SAGE KE Home > Literature & News > News Focus > Davenport, p. nf24
Article Views
Abstract
Full Text (HTML)
Article Tools
Download Citation
Post to CiteULike
Get Permission
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Related Content
Similar Articles In:
SAGE KE
PubMed
Search Google Scholar
for:
Articles by Davenport,
R. J.
Search PubMed for:
Articles by Davenport,
R. J.
Find Citing Articles in:
Google Scholar
Help & Feedback
News Focus Archive
Literature Help
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Sci. Aging Knowl. Environ., 30 March 2005
Vol. 2005, Issue 13, p. nf24
[DOI: 10.1126/sageke.2005.13.nf24]
NEWS FOCUS
Feeling Spunky With JNK
Protein funnels stress signals into insulin pathway and extends life
R. John Davenport
http://sageke.sciencemag.org/cgi/content/full/2005/13/nf24
Only a masochist would choose a life of stress and starvation, yet organisms can last unusually long if they exploit
molecular pathways that respond to these pressures. Now, scientists reveal how one molecule connects two such
pathways and lengthens the lives of worms and flies. The protein is linked to diabetes in mammals, suggesting
that what benefits invertebrates might not be good for humans. Researchers need to probe deeper to understand
how it shapes mammalian longevity, experts say.
When nutrients are abundant, the insulin and insulin-like growth factor 1 signaling pathways in mammals spur
cells to absorb sugar and grow. During lean times, the pathways shut down, and cells enter survival mode.
Blocking an analogous pathway in flies and worms extends longevity. The long-lived animals are often better at
resisting stresses such as oxidizing chemicals. Two years ago, geneticist Heinrich Jasper of the University of
Rochester in New York and colleagues found that an extra shot of a protein called JNK fortifies flies against
oxidative stress and prolongs survival. Now, two teams of researchers have investigated how JNK influences
insulin-related signaling.
Geneticist Heidi Tissenbaum of the University of Massachusetts Medical School in Worcester and colleagues
investigated JNK's contribution to nematode life span. Upping JNK production extended worm life by 40%, they
found. Blunting insulin-related signaling switches on a gene-control protein called FOXO. The researchers
discovered that worms with extra JNK but no functioning FOXO did not live long, suggesting that the two proteins
collaborate. Similarly, flies with hyperactive JNK only live long if they tote a full dose of FOXO, Jasper's team
found in a separate study. Further experiments by Tissenbaum's team bolster the connection: FOXO clings to JNK
in cultured cells engineered to produce both proteins.
FOXO switches on when it receives a phosphate group, which pushes the protein into the cell's nucleus. Jasper's
team observed that sparking fly insulin-like signaling restrained FOXO in the cytoplasm. But upon activation of
JNK, cells trucked FOXO to the nucleus. Similarly, Tissenbaum and colleagues found that nuclei contained more
of the protein when worms also carried extra JNK. In addition, her group reported that JNK stitches a phosphate
onto FOXO in a test tube. Together, the results suggest that JNK delays aging by activating FOXO.
The direct connection between JNK and FOXO is surprising, says diabetes researcher Morris White of Harvard
University. Diabetes researchers have investigated the JNK-insulin link and found that JNK squelches insulin
signaling, but it does so by inactivating components of the pathway other than FOXO. However, there are some
hints that the new findings will hold true in mammals. In November 2004, cell-signaling researcher Boudewijn
Burgering of the University of Utrecht in the Netherlands and colleagues reported that when mammalian cells are
exposed to oxidants, JNK phosphorylates a FOXO protein. The two new papers "provide the genetic data for our
biochemical analysis," says Burgering, making "quite a compelling case" that the proteins work together. Whether
JNK promotes long life in mammals is unclear. Nixing JNK fends off diabetes, says White, but vigorous JNK might
protect certain tissues. For instance, the protein might render muscle or fat insensitive to insulin, but it might stifle
insulin production in the pancreas, which can damage the organ if left unchecked. Clarifying JNK's contribution to
human aging might reveal a stress-free way for us to ride to long life.
March 30, 2005
1. M. A. Essers et al., FOXO transcription factor activation by oxidative stress mediated by the small GTPase
Ral and JNK. EMBO J. 23, 4802-4812 (2004). doi:10.1038/sj.emboj.7600476 [CrossRef][Medline][UMlinks]
2. S. W. Oh et al., JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of
ADVERTISEMENT
ADVERTISEMENT
To Advertise Find Products
AAAS.ORG FEEDBACK HELP LIBRARIANS Science Signaling ADVANCED
UNIVERSITY OF MASSACHUSETTS ALERTS | ACCESS RIGHTS | MY ACCOUNT | SIGN IN
SAGE KE Home Issue Archive Literature & News Community Resources Highlights About SAGE KE
Science Signaling
Science Translational Medicine
Enter Search Term](https://image.slidesharecdn.com/bea91817-ce34-477f-b0dd-ed602b2a3c31-160618000650/85/Science-News-Focus-2005-1-320.jpg)
![Feeling Spunky With JNK -- Davenport 2005 (13): nf24 -- <i>Science</i>'s SAGE KE
http://sageke.sciencemag.org.ezproxy.umassmed.edu/cgi/content/full/2005/13/nf24[4/11/2011 12:14:17 PM]
forkhead transcription factor/DAF-16. Proc. Natl. Acad. Sci. U.S.A. 102, 4494-4499 (2005). doi:
10.1073/pnas.0500749102 [Abstract/Free Full Text]
3. M. C. Wang, D. Bohmann, H. Jasper, JNK extends life span and limits growth by antagonizing cellular and
organism-wide responses to insulin signaling. Cell, 24 March 2005 [e-pub ahead of print]. [Abstract] [PDF]
doi:10.1016/S0092867405001972
Citation: R. J. Davenport, Feeling Spunky With JNK. Sci. Aging Knowl. Environ. 2005 (13),
nf24 (2005).
Science of Aging Knowledge Environment. ISSN 1539-6150
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