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PreprintCited by 3Protein Degradation and InhibitorsUbiquitin and proteasome pathwaysHeat shock proteins research

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Specific proteolysis mediated by a p97-directed proteolysis-targeting chimera (PROTAC)

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Salinas-Rebolledo, Constanza, Blesa, Javier, Valenzuela-Nieto, Guillermo, Schwefel, David, del Rey, Natalia López González, Méndez-Ruette, Maxs, Burkhalter, Janine, Bátiz, Luis Federico, Jara, Ronald, Obeso, José A., Chana-Cuevas, Pedro, Sapkota, Gopal P., Rojas-Fernandez, Alejandro·2024·eLife
DOI 10.1101/2024.03.08.584142PMC PMC12755880

Preprint — published as 10.7554/elife.101496 · Paper page

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Abstract

The p97 protein is a member of the AAA + family of ATPases. It is a mechanoenzyme that uses energy from ATP hydrolysis to promote protein unfolding and segregation actively. The unfolded products of p97 are presented to the 26S Proteasome for degradation. p97 substrate recognition is mediated by adaptors, which interact with substrates directly or indirectly through ubiquitin modifications, resulting in substrate funnelling into the central pore of the p97 hexamer and unfolding. We have engineered synthetic adaptors to target specific substrates to p97, using the extraordinary intracellular binding capabilities of camelid nanobodies fused to the UBX domain of the p97 Adapter FAF1. In such a way, we created a p97-directed proteolysis-targeting chimera (PROTAC), representing a unique E3 ubiquitin ligase-independent strategy to promote specific proteolysis.

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  1. 10.1001/archopht.1974.01010010055013 · DOI
  2. 10.1016/0092-8674(94)90396-4 · DOI
  3. 10.1038/35086067 · DOI · Paper page
  4. 10.1038/s41418-020-00706-7 · DOI
  5. 10.1038/nchembio.1858 · DOI · Paper page
  6. 10.1073/pnas.141230798 · DOI · Paper page
  7. 10.1073/pnas.1216880109 · DOI
  8. 10.1016/j.chembiol.2020.06.012 · DOI
  9. 10.21769/BioProtoc.2614 · DOI
  10. 10.1038/s41596-018-0028-3 · DOI
  11. 10.1038/s41573-021-00371-6 · DOI · Paper page
  12. 10.1002/anie.201706529 · DOI · Paper page
  13. 10.1016/j.bmc.2021.116221 · DOI
  14. 10.1080/21548331.1986.11704941 · DOI
  15. 10.1016/j.molcel.2020.04.032 · DOI
  16. 10.1016/j.cbpa.2019.02.022 · DOI
  17. 10.1016/j.apsb.2019.08.001 · DOI · Paper page
  18. 10.1038/s41573-021-00371-6 · DOI · Paper page
  19. 10.1038/nsmb.2180 · DOI · Paper page
  20. 10.1098/rsob.160255 · DOI · Paper page
  21. 10.1098/rsob.170066 · DOI · Paper page
  22. 10.1016/j.chembiol.2020.06.013 · DOI
  23. 10.1021/acschembio.7b00485 · DOI · Paper page
  24. 10.1038/s41467-018-08027-7 · DOI · Paper page
  25. 10.1016/j.molcel.2017.10.028 · DOI
  26. 10.1016/j.str.2013.08.017 · DOI
  27. 10.1038/s42003-019-0283-z · DOI
  28. 10.1016/j.cell.2017.04.020 · DOI
  29. 10.1016/j.molcel.2020.06.023 · DOI
  30. 10.1016/j.sbi.2023.102735 · DOI
  31. 10.1242/jcs.254201 · DOI
  32. 10.1038/s41467-023-36058-2 · DOI
  33. 10.1002/1873-3468.13213 · DOI
  34. 10.3389/fmolb.2017.00039 · DOI
  35. 10.1042/BST0360062 · DOI
  36. 10.1016/j.bbamcr.2011.09.006 · DOI
  37. 10.1186/1741-7007-10-48 · DOI
  38. 10.1042/bcj20160783 · DOI
  39. 10.7554/eLife.32866 · DOI
  40. 10.15252/embr.201947728 · DOI
  41. 10.1038/s41598-017-10506-8 · DOI
  42. 10.1038/sj.cdd.4400907 · DOI
  43. 10.1016/s0304-3940(03)00280-5 · DOI
  44. 10.1111/febs.13722 · DOI
  45. 10.1111/j.1365-2443.2007.01099.x · DOI
  46. 10.1038/s41598-020-57938-3 · DOI
  47. 10.1038/ng1332 · DOI · Paper page
  48. 10.1016/j.jocn.2019.03.063 · DOI
  49. 10.1093/brain/awu224 · DOI
  50. 10.1212/WNL.0b013e318275963b · DOI
  51. 10.1016/s0753-9053(05)80046-8 · DOI
  52. 10.1007/s10495-010-0466-z · DOI
  53. 10.1073/pnas.1530212100 · DOI
  54. 10.1038/embor.2010.49 · DOI
  55. 10.1016/j.jbc.2021.101187 · DOI
  56. 10.1016/j.cell.2017.04.020 · DOI
  57. 10.1002/pro.519 · DOI
  58. 10.1038/s41556-019-0392-4 · DOI · Paper page
  59. 10.1038/s41467-022-28019-y · DOI
  60. 10.1038/ncb2201 · DOI
  61. 10.1038/s41582-022-00642-9 · DOI · Paper page
  62. 10.1038/s41583-021-00542-9 · DOI · Paper page
  63. 10.1038/nm1066 · DOI · Paper page
  64. 10.1080/17460441.2019.1659242 · DOI
  65. 10.1016/j.tibs.2019.04.007 · DOI
  66. 10.1006/exnr.2000.7527 · DOI · Paper page
  67. 10.1136/jmg.36.10.739 · DOI
  68. 10.1371/journal.pone.0165964 · DOI
  69. 10.1002/pro.3412 · DOI
  70. 10.1038/s41531-018-0062-4 · DOI
  71. 10.1016/j.jmb.2013.01.040 · DOI
  72. 10.1038/emm.2004.1 · DOI
  73. 10.1016/j.cmet.2020.08.002 · DOI · Paper page
  74. 10.1016/j.bbrep.2016.10.010 · DOI
  75. 10.1038/s12276-019-0233-3 · DOI · Paper page
  76. 10.1126/science.1073440 · DOI · Paper page
  77. 10.1016/j.apsb.2015.05.007 · DOI · Paper page
  78. 10.1371/journal.pone.0169054 · DOI
  79. 10.3390/life11070607 · DOI
  80. 10.1146/annurev-pathmechdis-051222-120750 · DOI
  81. 10.3233/JPD-181471 · DOI
  82. 10.1002/mds.27360 · DOI
  83. 10.1101/2021.07.12.452081 · DOI
  84. 10.1038/s41392-019-0101-6 · DOI
  85. 10.1126/science.3140379 · DOI
  86. 10.1038/srep09811 · DOI
  87. 10.1371/journal.pone.0109752 · DOI
  88. 10.3389/fnagi.2021.698979 · DOI
  89. 10.1111/nan.12812 · DOI
  90. 10.1101/2021.08.15.456425 · DOI · Paper page
  91. 10.1016/j.str.2011.03.018 · DOI
  92. 10.1038/s41467-020-20359-x · DOI
  93. 10.1107/S0907444910007493 · DOI · Paper page

Metadata

Authors
Salinas-Rebolledo, C., Blesa, J., Valenzuela-Nieto, G., Schwefel, D., del Rey, N. L. G., Méndez-Ruette, M., Burkhalter, J., Bátiz, L. F., Jara, R., Obeso, J. A., Chana-Cuevas, P., Sapkota, G. P., & Rojas-Fernandez, A.
Affiliations
  • Austral University of Chile (CL)
  • HM Hospitales (ES)
  • Technische Universität Berlin (DE)
  • Universidad de Los Andes (CO)
  • University of Dundee (GB)
ORCID
Venue
eLife
Publisher
openRxiv
Published
2024-03-09
Volume
14
ISSN
2050-084X (ISSN-L)
DOI
10.1101/2024.03.08.584142
PMC
PMC12755880
OpenAlex
W4416723086
Cited by
3
References
1
Citations by year
2026: 3
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Discovery Research Portal (University of Dundee) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Comunidad de Madrid (S2017/BMD-3700, S2017/BMD)
  • Deutsche Forschungsgemeinschaft
  • Swedish Foundation for International Cooperation in Research and Higher Education
  • Max-Planck-Gesellschaft (190011)
  • Agencia Nacional de Investigación y Desarrollo (MPG190011, 190011, 13220075, 3220635, T010047, 1200427, 21170632, FB210008)
  • Instituto de Salud Carlos III (CP19/00200, PI20/00496, FIS PI20/00496)
  • Fondo Nacional de Desarrollo Científico y Tecnológico (13220075, 3220635, 1200427)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
VCP, PROTACs, FAF1, UBX domain, camelid nanobodies, protein unfolding, 26S proteasome, substrate recognition, ATPase
MeSH terms
Valosin Containing Protein, Adenosine Triphosphatases, Humans, Recombinant Fusion Proteins, Adaptor Proteins, Signal Transducing, Proteolysis, Single-Domain Antibodies

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