Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
Perspective

The discovery of ubiquitin-dependent proteolysis

Keith D. Wilkinson
  1. Department of Biochemistry, Emory University School of Medicine, 4017 Rollins Research Building, 1510 Clifton Road, Atlanta, GA 30322

See allHide authors and affiliations

PNAS October 25, 2005 102 (43) 15280-15282; first published October 17, 2005; https://doi.org/10.1073/pnas.0504842102
Keith D. Wilkinson
Department of Biochemistry, Emory University School of Medicine, 4017 Rollins Research Building, 1510 Clifton Road, Atlanta, GA 30322
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  1. Edited by Marc W. Kirschner, Harvard Medical School, Boston, MA (received for review June 9, 2005)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Abstract

In early 1980, Irwin A. Rose, Avram Hershko, and Aaron Ciechanover published two papers in PNAS that reported the astounding observation that energy-dependent intracellular proteolysis was far more complicated than the previously accepted models of lysosomal proteolysis or the action of ATP-dependent proteases such as bacterial lon. In fact, it has turned out to be even more complicated than they could have suspected. The general model of covalently attaching a small protein as a targeting signal has proved to be every bit as important to eukaryotic cells as the better understood modifications such as phosphorylation or acetylation. The key player in this modification, a small protein called ubiquitin (APF-1 in these papers), is the founding member of a large family of proteins containing the β-grasp fold and is used as a posttranslational targeting signal to modify the structure, function, and/or localization of other proteins. The story of this discovery is a textbook example of the confluence of intellectual curiosity, unselfish collaboration, chance, luck, and preparation.

It is a truism in science that the first example of any biological phenomenon is the hardest to prove. We rely so much on precedent to formulate our hypothesis that something truly unique and novel is often over-looked for many years. The covalent modification of proteins by the attachment of other proteins is one such example (1–6). As we now know, this modification is a targeting mechanism used to move proteins around in the cell. The ubiquitin family of modifiers (ubiquitin, Nedd8, SUMO, ISG15, etc.) has been implicated in the regulation of proteolysis, nuclear localization, chromatin structure, genetic integrity, protein quality control, and signaling (6). The prototypical example of this modification is the covalent attachment of ubiquitin to proteins to target them for degradation by the proteasome and was first reported in two PNAS papers published early in 1980 by the 2004 Nobel laureates in chemistry, Avram Hershko, Aaron Ciechanover, and Irwin A. Rose (Fig. 1), and their collaborators (1, 7). These two papers outlined the essentials of the system and were amazingly prescient in their interpretations and predictions based on simple biochemical analysis.

Fig. 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Fig. 1.

The laureates at the Karolinska Institute after their Nobel addresses. Shown are (left to right) Aaron Ciechanover, Irwin Rose, and Avram Hershko.

The authors set out to explain a simple biological curiosity: the fact that intracellular proteolysis in mammalian cells requires energy. Melvin Simpson first showed this in his 1953 studies with isotopic labeling of cellular proteins (8), and for the next 25 years there were few insights into the mechanisms or metabolic logic of this observation. The hydrolysis of the peptide bond is exergonic, and there is no thermodynamic reason to use energy. The apparent requirement for energy could mean only that there was something we didn't understand. Part of the answer began to become apparent in the mid 1970s when Goldberg's group showed that damaged or abnormal proteins were rapidly cleared from the cell (9–11). He and Schimke (11) pointed out that enzymes that catalyzed rate-limiting steps in metabolic pathways were generally short-lived and that their amounts were responsive to metabolic conditions. Thus, by the late 1970s, we began to suspect that the energy dependence of intracellular proteolysis reflected some energy-dependent regulation of proteolytic systems.

The collaboration of Ciechanover, Hershko, and Rose was uniquely positioned and qualified to define this regulation. Avram Hershko (M.D. 1965 and Ph.D. 1969 from Hebrew University-Hadassah Medical School) did postdoctoral work in the laboratory of Gordon Tompkins at the University of California at San Francisco where he first became interested in protein degradation. His early studies were on tyrosine amino transferase and on the rates of bulk protein turnover in bacteria and mammalian cells. Hershko then established his own laboratory at the Technion-Israel Institute of Technology in Haifa and continued to collaborate with Tompkins until his untimely death in 1975. Aaron Ciechanover (M.D. 1974 and Ph.D. 1981 from Hebrew University-Hadassah Medical School) completed his military service before joining Hershko as a graduate student at the Technion-Israel Institute of Technology. Irwin A. “Ernie” Rose (Ph.D. in 1952 from the University of Chicago) did postdoctoral studies with Charles Carter at Case Western Reserve University and Severo Ochoa at New York University. He joined the Department of Pharmacology at Yale University in 1954 and moved to the Institute for Cancer Research at the Fox Chase Cancer Center in 1963. As a mechanistic enzymologist, he gained fame for his studies on proton transfer reactions and the use of isotopic labeling to examine the chemical mechanisms used by enzymes. Rose's interest in protein degradation dated back to the observations of Simpson, his colleague at Yale, who had demonstrated the ATP dependence of proteolysis in 1953. They talked often about this biochemical curiosity, and Rose would come back to this question periodically, but made little progress. Hershko and Rose first met at a Fogarty Foundation meeting in 1977 where they discovered their mutual interests in ATP-dependent proteolysis. Rose invited Hershko to do a sabbatical in his laboratory at the Institute for Cancer Research in Philadelphia. This began a 10-year collaboration that saw Rose hosting the Israeli group every summer. Rose was a patron and intellectual contributor far beyond what might be indicated by his authorship on the papers of that era. Thus, these two talented investigators entered into the collaboration that would define one of the several mechanisms of ATP-dependent protein degradation and frame a new means of viewing cellular regulation. [See Ciechanover (12) and Goldberg (13) for a more complete discussion of the various ATP-dependent processes.]

By 1979, Hershko and Ciechanover had exploited the seminal observations of Etlinger and Goldberg that reticulocyte lysates (which lack lysosomes) exhibited ATP-dependent proteolysis of denatured proteins (14) and would be amenable to biochemical fractionation. Hershko and Ciechanover first showed the system could be separated into two fractions (I and II) that had to be recombined to generate ATP-dependent proteolysis (15). Fraction I contained a single required component, a small, heat-stable protein they termed APF-1 (ATP-dependent proteolysis factor 1 because it was the first factor to be characterized). They then went on to further analyze fraction II and discovered a high molecular weight fraction (APF-2) that was stabilized by ATP and required for reconstitution of the ATP-dependent proteolysis (16). In retrospect, APF-1 was ubiquitin and APF-2 was probably the active protease, the 26S proteasome. At the time, however, Hershko, Ciechanover, and Rose considered that APF-2 might contain a kinase domain that phosphorylated APF-1 or an ATP-dependent binding protein that interacted with APF-1. Thus, the work reported in the cited PNAS papers (1, 7) began as an attempt to see whether there was an ATP-dependent association of APF-1 with other components of the system.

In the first paper (1), Ciechanover et al. showed that 125I-labeled APF-1 was promoted to a high molecular weight form upon incubation with fraction II and ATP. This association required low concentrations of ATP and was reversed upon removal of the ATP. At this time, a postdoctoral fellow in Rose's laboratory, Art Haas, began to characterize this association, and he found that the complex survived high pH. To everyone's surprise, the association of 125I-labeled APF-1 with proteins in fraction II was covalent! They went on to show that the bond was stable to NaOH treatment and that APF-1 was bound to many different proteins as judged by SDS/PAGE. The authors concluded that it was likely that conjugation was required for proteolysis; the nucleotide and metal ion requirements were similar for conjugation and proteolysis, as were the amounts of ATP and fraction II necessary to maximally stimulate. The covalent attachment of APF-1 to cellular proteins also explained why some investigators had so much difficulty demonstrating a requirement for APF-1 in ATP dependent proteolysis. When fraction II was prepared from reticulocytes without first depleting the ATP, most of the APF-1 was initially present in high molecular weight conjugates that were subsequently found in fraction II. These conjugates were rapidly disassembled by amidases in fraction II, thereby liberating free APF-1. Thus, there was sufficient APF-1 in fraction II to support proteolysis. If one first depleted the ATP, APF-1 was liberated before the chromatographic preparation of fraction II and APF-1 had to be added back to obtain maximal rates of proteolysis. This series of rather simple experiments convincingly demonstrated that APF-1 was covalently linked to multiple proteins in fraction II and that the linkage was reversible, although they did not demonstrate that this reaction was required for proteolysis. It was also not clear whether the modified proteins were enzymes of the system or substrates destined for degradation.

This paper was profoundly important to me, as well as to many others. At the time this work was being conducted, I was a postdoctoral fellow in Rose's laboratory and was being recruited to identify APF-1. One evening at a local establishment, Haas and I discussed these results with Michael Urban, a postdoctoral fellow from the next laboratory. He pointed out that this covalent attachment of two proteins was unusual, but not without precedent. Goldknopf and Busch (2) had shown that histone H2a was covalently modified by the attachment of a small protein called ubiquitin. Gideon Goldstein first discovered ubiquitin in his search for thymopoietin (17), and he generously shared authentic samples with me. Intrigued by this similarity, Urban, Haas, and I went on to show that APF-1 was the previously known protein called ubiquitin (18). Although it was known that ubiquitin was widely distributed, its physiological role was unclear until the 1980 PNAS papers suggested its role in ATP-dependent proteolysis (1, 7).

To ask whether this covalent bond formation was related to proteolysis, Hershko et al. (7) next went on to show that authentic substrates of the system were heavily modified and that multiple molecules of APF-1 were attached to each molecule of substrate (Fig. 2). These experiments demonstrated many elements of the system. The conjugation seemed to be enzyme-catalyzed, demonstrating for the first time the activity of ubiquitin ligases (19–22). The ligase activity was processive, preferring to add additional ubiquitin molecules to existing conjugates even in the presence of excess free substrate. Recent proteomics analyses suggest that there are hundreds of such ligases of at least two different types (21, 22). Thus, it seems likely that multiple ligases were active in fraction II and that this might explain why so many different proteins were ubiquitinated. Nearly 10 years later, Chau et al. (23) showed that substrates for proteolysis were polyubiquitinated, forming a chain linked through K48 of one ubiquitin and the C terminus of the next. Pioneering work out of the Finley and the Ellison laboratories later showed that other types of polyubiquitin chains also exist and that they are required in nonproteolytic pathways (24, 25).

Fig. 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Fig. 2.

Formation of covalent compounds between APF-1 and lysozyme in an ATP-dependent reaction. Tracks 1–5, compound formation with 125I-APF-1; track 1, without ATP; track 2, with ATP; tracks 3–5, with ATP and 5, 10, or 25 mg of unlabeled lysozyme, respectively; and tracks 6 and 7, compound formation with 125I-lysozyme. Conditions were as detailed in Methods of ref. 7, except that 5 μgof 125I-lysozyme (40,000 cpm) and 3 μgof unlabeled APF-1 were used. Track 6, ATP omitted; track 7, with 2 mM ATP. Contamination in 125I-labeled lysozyme is indicated. [Reproduced with permission from ref. 7 (Copyright 1980).]

Hershko et al. (7) then followed up on the observation that conjugation was reversed upon removal of ATP by demonstrating an enzyme-catalyzed disassembly of conjugates and liberation of intact ubiquitin that could be used for another round of conjugation (see figure 5 in ref. 7). Thus, they demonstrated the presence of specific amidases, or deubiquitinating enzymes as we now know them (26, 27), that accurately reversed conjugation. They pointed out the possibility that these could be “correction enzymes,” whose role we now understand as similar to the role of phosphatases in a kinase/phosphatase cycle. I shamelessly appropriated this idea upon taking my first job at Emory University and developed an assay for these amidases (deubiquitinating enzymes). We purified and cloned the first of these important regulatory enzymes from mammals (28), whereas Miller et al. (29) cloned Yuh1, the homologous protein from yeast. The elegant work of Varshavsky and his colleagues (30) in the yeast system soon followed, and in the ensuing years we have learned that there are >80 of these enzymes in at least six distinct gene families that regulate vital aspects of ubiquitination.

Thus, this second PNAS paper (7) concluded with a simple scheme outlining important aspects of ubiquitin-dependent proteolysis (Fig. 3). Ligases, deubiquitinating enzymes, and a specific protease were all predicted based on these biochemical assays. This has been an amazingly durable representation of the system, requiring only elaboration as details emerge. At its simplest, it pointed out that covalent attachment of ubiquitin targets proteins for delivery to a protease, thus resulting in the degradation of the target protein and release of free ubiquitin for another catalytic cycle. The protease turned out to be the proteasome, to be ATP-dependent, and to produce peptides and not amino acids. But it also explained the chemistry of other ubiquitin-like modifications (1–6). Modification of proteins by a single ubiquitin targets proteins in the endocytic pathway and in chromatin remodeling. Modification by SUMO is involved in altering the enzymatic activities of modified proteins or in targeting proteins to specific locations within the nucleus. Modification of cullins by Nedd8 helps to assemble active enzyme complexes. We need only to change the identity of the ubiquitin-like protein in step 1 and the consequences of the modification in step 3 to make this scheme completely general. There are even amidases that reverse the conjugation of ubiquitin-like proteins, accounting for steps 2 and 4 (31–33).

Fig. 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Fig. 3.

Proposed sequence of events in ATP-dependent protein breakdown (see the text). 1, APF-1-protein amide synthetase (acting on lysine ε-NH2 groups). 2, Amidase that allows correction when n = 1 or 2. 3, Peptidases that act strongly on (APF-1)n derivatives, when n > 1 or 2. 4, Amidase for APF-1-X; X is lysine or a small peptide. [Reproduced with permission from ref. 7 (Copyright 1980).]

These papers drew powerful conclusions from fairly simple biochemical experiments, but at the time there was considerable skepticism of this new paradigm. As Hershko subsequently showed, these conclusions were largely correct (34) and both of these PNAS contributions were extremely influential, being in the top ten (based on citations) of Hershko's original research publications. Their predictions and models have withstood the test of time and are a tribute to the imagination and clarity that Hershko, Ciechanover, and Rose have brought to the field of ubiquitin-dependent metabolism.

Footnotes

    • ↵* E-mail: keith.wilkinson{at}emory.edu.

    • Author contributions: K.D.W. wrote the paper.

    • Received June 9, 2005.
    • Accepted August 29, 2005.
    • Copyright © 2005, The National Academy of Sciences

    References

    1. ↵
      Ciechanover, A., Heller, H., Elias, S., Haas, A. L. & Hershko, A. (1980) Proc. Natl. Acad. Sci. USA 77, 1365-1368.pmid:6769112
      OpenUrlAbstract/FREE Full Text
    2. ↵
      Goldknopf, I. L. & Busch, H. (1977) Proc. Natl. Acad. Sci. USA 74, 864-868.pmid:265581
      OpenUrlAbstract/FREE Full Text
    3. Mahajan, R., Delphin, C., Guan, T., Gerace, L. & Melchior, F. (1997) Cell 88, 97-107.pmid:9019411
      OpenUrlCrossRefPubMed
    4. Kamitani, T., Kito, K., Nguyen, H. P. & Yeh, E. T. (1997) J. Biol. Chem. 272, 28557-28562.pmid:9353319
      OpenUrlAbstract/FREE Full Text
    5. Ohsumi, Y. (2001) Nat. Rev. Mol. Cell Biol. 2, 211-216.pmid:11265251
      OpenUrlCrossRefPubMed
    6. ↵
      Schwartz, D. C. & Hochstrasser, M. (2003) Trends Biochem. Sci. 28, 321-328.pmid:12826404
      OpenUrlCrossRefPubMed
    7. ↵
      Hershko, A., Ciechanover, A., Heller, H., Haas, A. L. & Rose, I. A. (1980) Proc. Natl. Acad. Sci. USA 77, 1783-1786.pmid:6990414
      OpenUrlAbstract/FREE Full Text
    8. ↵
      Simpson, M. V. (1953) J. Biol. Chem. 201, 143-154.pmid:13044783
      OpenUrlFREE Full Text
    9. ↵
      Goldberg, A. L. & Dice, J. F. (1974) Annu. Rev. Biochem. 43, 835-869.pmid:4604628
      OpenUrlCrossRefPubMed
    10. Goldberg, A. L. & St. John, A. C. (1976) Annu. Rev. Biochem. 45, 747-803.pmid:786161
      OpenUrlCrossRefPubMed
    11. ↵
      Schimke, R. T. (1976) Circ. Res. 38, I131-7.pmid:1269088
      OpenUrlCrossRefPubMed
    12. ↵
      Ciechanover, A. (2005) Nat. Rev. Mol. Cell Biol. 6, 79-87.pmid:15688069
      OpenUrlCrossRefPubMed
    13. ↵
      Goldberg, A. L. (2005) Neuron 45, 339-344.pmid:15694320
      OpenUrlCrossRefPubMed
    14. ↵
      Etlinger, J. D. & Goldberg, A. L. (1977) Proc. Natl. Acad. Sci. USA 74, 54-58.pmid:264694
      OpenUrlAbstract/FREE Full Text
    15. ↵
      Ciehanover, A., Hod, Y. & Hershko, A. (1978) Biochem. Biophys. Res. Commun. 81, 1100-1105.pmid:666810
      OpenUrlCrossRefPubMed
    16. ↵
      Hershko, A., Ciechanover, A. & Rose, I. A. (1979) Proc. Natl. Acad. Sci. USA 76, 3107-3110.pmid:290989
      OpenUrlAbstract/FREE Full Text
    17. ↵
      Goldstein, G., Scheid, M., Hammerling, U., Schlesinger, D. H., Niall, H. D. & Boyse, E. A. (1975) Proc. Natl. Acad. Sci. USA 72, 11-15.pmid:1078892
      OpenUrlAbstract/FREE Full Text
    18. ↵
      Wilkinson, K. D., Urban, M. K. & Haas, A. L. (1980) J. Biol. Chem. 255, 7529-7532.pmid:6249803
      OpenUrlAbstract/FREE Full Text
    19. ↵
      Hershko, A. & Ciechanover, A. (1998) Annu. Rev. Biochem. 67, 425-479.pmid:9759494
      OpenUrlCrossRefPubMed
    20. Tanaka, K., Suzuki, T. & Chiba, T. (1998) Mol. Cells 8, 503-512.pmid:9856335
      OpenUrlPubMed
    21. ↵
      Pickart, C. M. (2001) Annu. Rev. Biochem. 70, 503-533.pmid:11395416
      OpenUrlCrossRefPubMed
    22. ↵
      Petroski, M. D. & Deshaies, R. J. (2005) Nat. Rev. Mol. Cell Biol. 6, 9-20.pmid:15688063
      OpenUrlCrossRefPubMed
    23. ↵
      Chau, V., Tobias, J. W., Bachmair, A., Marriott, D., Ecker, D. J., Gonda, D. K. & Varshavsky, A. (1989) Science 243, 1576-1583.pmid:2538923
      OpenUrlAbstract/FREE Full Text
    24. ↵
      Spence, J., Sadis, S., Haas, A. L. & Finley, D. (1995) Mol. Cell. Biol. 15, 1265-1273.pmid:7862120
      OpenUrlAbstract/FREE Full Text
    25. ↵
      Arnason, T. & Ellison, M. J. (1994) Mol. Cell. Biol. 14, 7876-7883.pmid:7969127
      OpenUrlAbstract/FREE Full Text
    26. ↵
      Amerik, A. Y. & Hochstrasser, M. (2004) Biochim. Biophys. Acta 1695, 189-207.pmid:15571815
      OpenUrlCrossRefPubMed
    27. ↵
      Wilkinson, K. D. (1997) FASEB J. 11, 1245-1256.pmid:9409543
      OpenUrlAbstract
    28. ↵
      Wilkinson, K. D., Lee, K. M., Deshpande, S., Duerksen-Hughes, P., Boss, J. M. & Pohl, J. (1989) Science 246, 670-673.pmid:2530630
      OpenUrlAbstract/FREE Full Text
    29. ↵
      Miller, H. I., Henzel, W. J., Ridgeway, J. B., Kuang, W., Chisholm, V. & Liu, C. (1989) Biotechnology 7, 698-704.
      OpenUrlCrossRef
    30. ↵
      Baker, R. T., Tobias, J. W. & Varshavsky, A. (1992) J. Biol. Chem. 267, 23364-23375.pmid:1429680
      OpenUrlAbstract/FREE Full Text
    31. ↵
      Li, S. J. & Hochstrasser, M. (1999) Nature 398, 246-251.pmid:10094048
      OpenUrlCrossRefPubMed
    32. Gan-Erdene, T., Nagamalleswari, K., Yin, L., Wu, K., Pan, Z. Q. & Wilkinson, K. D. (2003) J. Biol. Chem. 278, 28892-28900.pmid:12759362
      OpenUrlAbstract/FREE Full Text
    33. ↵
      Malakhov, M. P., Malakhova, O. A., Kim, K. I., Ritchie, K. J. & Zhang, D. E. (2002) J. Biol. Chem. 277, 9976-9981.pmid:11788588
      OpenUrlAbstract/FREE Full Text
    34. ↵
      Hershko, A., Heller, H., Elias, S. & Ciechanover, A. (1983) J. Biol. Chem. 258, 8206-8214.pmid:6305978
      OpenUrlAbstract/FREE Full Text
    PreviousNext
    Back to top
    Article Alerts
    Email Article

    Thank you for your interest in spreading the word on PNAS.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    The discovery of ubiquitin-dependent proteolysis
    (Your Name) has sent you a message from PNAS
    (Your Name) thought you would like to see the PNAS web site.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Citation Tools
    The discovery of ubiquitin-dependent proteolysis
    Keith D. Wilkinson
    Proceedings of the National Academy of Sciences Oct 2005, 102 (43) 15280-15282; DOI: 10.1073/pnas.0504842102

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    Request Permissions
    Share
    The discovery of ubiquitin-dependent proteolysis
    Keith D. Wilkinson
    Proceedings of the National Academy of Sciences Oct 2005, 102 (43) 15280-15282; DOI: 10.1073/pnas.0504842102
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
    • Tweet Widget
    • Facebook Like
    • Mendeley logo Mendeley
    Proceedings of the National Academy of Sciences: 102 (43)
    Table of Contents

    Submit

    Sign up for Article Alerts

    Jump to section

    • Article
      • Abstract
      • Footnotes
      • References
    • Figures & SI
    • Info & Metrics
    • PDF

    You May Also be Interested in

    Smoke emanates from Japan’s Fukushima nuclear power plant a few days after tsunami damage
    Core Concept: Muography offers a new way to see inside a multitude of objects
    Muons penetrate much further than X-rays, they do essentially zero damage, and they are provided for free by the cosmos.
    Image credit: Science Source/Digital Globe.
    Water from a faucet fills a glass.
    News Feature: How “forever chemicals” might impair the immune system
    Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
    Image credit: Shutterstock/Dmitry Naumov.
    Venus flytrap captures a fly.
    Journal Club: Venus flytrap mechanism could shed light on how plants sense touch
    One protein seems to play a key role in touch sensitivity for flytraps and other meat-eating plants.
    Image credit: Shutterstock/Kuttelvaserova Stuchelova.
    Illustration of groups of people chatting
    Exploring the length of human conversations
    Adam Mastroianni and Daniel Gilbert explore why conversations almost never end when people want them to.
    Listen
    Past PodcastsSubscribe
    Horse fossil
    Mounted horseback riding in ancient China
    A study uncovers early evidence of equestrianism in ancient China.
    Image credit: Jian Ma.

    Similar Articles

    Site Logo
    Powered by HighWire
    • Submit Manuscript
    • Twitter
    • Facebook
    • RSS Feeds
    • Email Alerts

    Articles

    • Current Issue
    • Special Feature Articles – Most Recent
    • List of Issues

    PNAS Portals

    • Anthropology
    • Chemistry
    • Classics
    • Front Matter
    • Physics
    • Sustainability Science
    • Teaching Resources

    Information

    • Authors
    • Editorial Board
    • Reviewers
    • Subscribers
    • Librarians
    • Press
    • Cozzarelli Prize
    • Site Map
    • PNAS Updates
    • FAQs
    • Accessibility Statement
    • Rights & Permissions
    • About
    • Contact

    Feedback    Privacy/Legal

    Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490