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

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1. 

   Version published to 10.7554/elife.101496 on eLife

   Nov 26, 2025
2. 

   Review Commons

   Jul 11, 2024

   Note: This response was posted by the corresponding author to Review Commons. The content has not been altered except for formatting.

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   Reply to the reviewers

   Reviewer #1 (Evidence, reproducibility and clarity (Required)):

   The paper by Salinas-Rebolledo et al. describes a novel PROTAC approach in which the UBX domain of FAF1 is fused to a nanobody that recognizes the target protein. The idea is that the UBX domain will bind the fusion protein to the p97 ATPase, a major ATPase involved in the unfolding of many proteins. The target protein recognized by the UBX-nanobody fusion (UBX-Nb) is then supposed to be unfolded in a ubiquitin-independent manner and subsequently degraded by the proteasome.

   The authors provide evidence that Ubx-Nb, containing a nanobody recognizing GFP, can colocalize with GFP fusion …

   Note: This response was posted by the corresponding author to Review Commons. The content has not been altered except for formatting.

   Learn more at Review Commons

   ---

   Reply to the reviewers

   Reviewer #1 (Evidence, reproducibility and clarity (Required)):

   The paper by Salinas-Rebolledo et al. describes a novel PROTAC approach in which the UBX domain of FAF1 is fused to a nanobody that recognizes the target protein. The idea is that the UBX domain will bind the fusion protein to the p97 ATPase, a major ATPase involved in the unfolding of many proteins. The target protein recognized by the UBX-nanobody fusion (UBX-Nb) is then supposed to be unfolded in a ubiquitin-independent manner and subsequently degraded by the proteasome.

   The authors provide evidence that Ubx-Nb, containing a nanobody recognizing GFP, can colocalize with GFP fusion proteins in the nucleus and to liquid-liquid phase separation structures. Importantly, the fusion can reduce the cellular levels of the target proteins. The authors confirm that degradation triggered by Ubx-Nb is proteasome dependent. Ubx-Nb can also promote the degradation of model proteins that form aggregates relevant to neurodegenerative diseases.

   __* The major issue with the paper is that it does not provide mechanistic insight into the degradation mechanism. First, the data implicating p97 in degradation are conflicting. On the one hand, siRNA of p97 compromises degradation (although degradation is not completely inhibited; see Figure 4G), but on the other hand, an inhibitor of p97 does not have an effect. The authors have not shown that target proteins are actually unfolded by their artificial adaptor (in vitro experiments would be required). __

   __In addition, it would be important to show co-localization in vivo with p97. __

   Thus, the role of p97 is not convincingly established. Another major question is how the unfolded, non-ubiquitinated proteins would be degraded by the 26S proteasome. Is there a ubiquitin ligase required after substrate unfolding?

   Overall, the paper reports some intriguing effects of their designed PROTAC adaptor, but the mechanism by which it functions remains unclear. The findings of the manuscript appears too preliminary in its current version for it to be of value to the community.

   Responses #1

   We appreciate the detailed feedback provided and acknowledge the reviewers' concerns regarding the mechanistic insight into the degradation process. Below, we address each point raised:

   We acknowledge that our current data do not fully elucidate the degradation mechanism involving p97. Our preliminary findings suggest that while siRNA of p97 compromises degradation, this effect is not absolute. Additionally, we recognize the inconsistency observed with the p97 inhibitor, which did not affect degradation. It is important to note that the selective inhibitor used in our study binds to the D2 domains of p97, as reported by Zhou et al. (J Med Chem. 2015). There are molecules that bind to the D1 domain and enhance p97-mediated degradation (Figuerola-Conchas et al., ACS Chem Biol. 2020). The primary ATPase function of p97 is associated with the D2 domain, but ATP binding to the D1 domain is crucial for hexamer formation and N-terminal domain conformation, which regulates cofactor binding and various functions of p97. Therefore, it is possible that our p97-PROTAC activates the D1 domain or interacts with cofactors enhancing protein degradation mediated by p97.

   We plan to conduct in vitro experiments to demonstrate that target proteins are unfolded by our artificial adaptor. We have already cloned the degradation system into a bacterial expression vector to express and purify the system for these in vitro studies, which will be carried out in California. Furthermore, we aim to show in vivo co-localization with p97 in future studies.

   *We understand the importance of establishing the role of p97 convincingly. Our preliminary data indicate the presence of residual p97 in siRNA experiments. Regarding the degradation of unfolded, non-ubiquitinated proteins by the 26S proteasome, there are studies indicating that various proteins are degraded by the proteasome independently of ubiquitin. Moreover, evidence suggests that different pools of the same protein can be directed to the proteasome via both ubiquitin-dependent and ubiquitin-independent mechanisms under the same cellular conditions. Also, prior research by Butler et al. (2016) demonstrated that fusing NbSyn87 with the mouse Ornithine Decarboxylase (ODC) PEST degron effectively reduced protein levels and this reduction was achieved by harnessing the innate cellular machinery responsible for ubiquitin-independent proteolysis. *

   1. • Makaros Y, Raiff A, Timms RT, Wagh AR, Gueta MI, Bekturova A, Guez-Haddad J, Brodsky S, Opatowsky Y, Glickman MH, Elledge SJ, Koren I. Ubiquitin-independent proteasomal degradation driven by C-degron pathways. Mol Cell. 2023 Jun 1;83(11):1921-1935.e7. doi: 10.1016/j.molcel.2023.04.023. Epub 2023 May 17. PMID: 37201526; PMCID: PMC10237035.*
   2. • Butler DC, Joshi SN, Genst E, Baghel AS, Dobson CM, Messer A. Bifunctional Anti-Non-Amyloid Component α-Synuclein Nanobodies Are Protective In Situ. PLoS One. 2016 Nov 8;11(11):e0165964. doi: 10.1371/journal.pone.0165964. PMID: 27824888; PMCID: PMC5100967.*
   3. • Erales J, Coffino P. Ubiquitin-independent proteasomal degradation. Biochim Biophys Acta. 2014 Jan;1843(1):216-21. doi: 10.1016/j.bbamcr.2013.05.008. Epub 2013 May 14. PMID: 23684952; PMCID: PMC3770795.*
   4. • Donghong Ju, Youming Xie, Proteasomal Degradation of RPN4 via Two Distinct Mechanisms, Ubiquitin-dependent and -independent*, Journal of Biological Chemistry, Volume 279, Issue 23, 2004, Pages 23851-23854, ISSN 0021-9258.*

   We also speculate that the degradation may also occur via the autophagy-lysosome pathway. These speculations will be added to the discussion section, and we plan to investigate this pathway in detail in a subsequent scientific article focused on the mechanism of action of p97-PROTAC.

   We recognize the need for further mechanistic studies and plan to publish these preliminary findings while continuing our research to elucidate the degradation mechanism. Our future work includes determining the crystal structure and conducting mass spectrometry to identify other proteins interacting with this complex, potentially aiding in degradation. We also plan to test the system in vivo using murine models with alpha-synuclein overexpression, in collaboration with researchers in Spain. This long-term project will form the basis of a subsequent publication.

   We believe that our findings present an innovative and unique tool, and this preliminary data warrant publication. We appreciate the reviewers' comments and hope that our detailed response and future research plans address their concerns.

   Minor points:

   Fig. 1B: Although emerin is reported to be a nuclear envelope protein, it is not localized to the NE, but throughout the ER, likely because the protein was too highly expressed.

   We agree with the reviewer, the overexpression of the NE could leak into the ER. We do not have specific Nanobodies to directly degrade Emerin. However, we would like to make the point that in both cases the protein will conserve a single transmembrane domain and even then, the GFP Nanobody fused to the UBX domain is able to trigger degradation

   Fig. 1B: ETV co-localization is not obvious from the figure.

   We are going to repeating the experiment and quantify the colocalization as suggested

   ---

   Fig. 4: The depletion of p97 leads to cell death, so it is unclear whether the siRNA effect is specific.

   We appreciate your comment and would like to clarify that there are published studies where the p97 gene has been silenced in HeLa cells without causing complete cell death. While it is true that a significant number of cells die post-transfection, we have observed that by changing the cell culture medium daily, the remaining cells start to grow again.

   Studies supporting our findings include:

   1. • Wójcik C, Yano M, DeMartino GN. RNA interference of valosin-containing protein (VCP/p97) reveals multiple cellular roles linked to ubiquitin/proteasome-dependent proteolysis. J Cell Sci. 2004 Jan 15;117(Pt 2):281-92. doi: 10.1242/jcs.00841. Epub 2003 Dec 2. PMID: 14657277. *
   2. • Beskow A, Grimberg KB, Bott LC, Salomons FA, Dantuma NP, Young P. A conserved unfoldase activity for the p97 AAA-ATPase in proteasomal degradation. J Mol Biol. 2009 Dec 11;394(4):732-46. doi: 10.1016/j.jmb.2009.09.050. Epub 2009 Sep 24. PMID: 19782090.*
   3. • Yahiro K, Tsutsuki H, Ogura K, Nagasawa S, Moss J, Noda M. Regulation of subtilase cytotoxin-induced cell death by an RNA-dependent protein kinase-like endoplasmic reticulum kinase-dependent proteasome pathway in HeLa cells. Infect Immun. 2012 May;80(5):1803-14. doi: 10.1128/IAI.06164-11. Epub 2012 Feb 21. PMID: 22354021; PMCID: PMC3347452.* Additionally, although our figure does not clearly show the band corresponding to p97, upon overexposing the film, we can detect a very faint band of the protein. This indicates that there is still residual expression of p97, albeit at a lower concentration, which is consistent with a significant reduction but not a complete elimination of the protein.

   Fig. 5C: The colocalization of GFP-HTT Q23 with UBX-Nb(GFP) is not entirely convincing.

   We are going to repeating the experiment and quantify the colocalization as suggested

   Reviewer #1 (Significance (Required)):

   Overall, the paper reports some intriguing effects of their designed PROTAC adaptor, but the mechanism by which it functions remains unclear. The findings of the manuscript appears too preliminary in its current version for it to be of value to the community.

   Reviewer #2 (Evidence, reproducibility and clarity (Required)):

   Summary:

   The authors have developed a p97-directed proteolysis-targeting chimera (PROTAC) that operates independently of ubiquitin. This system employs a camelid nanobody to selectively recognize target proteins, tethered to p97 through the UBX domain of the p97 adapter FAF1. The anti-GFP nanobody effectively targets various GFP-fusion proteins for degradation via the proteasome, relying on p97 for its mechanism of action. The authors validate the presence of p97 in brain tissues of Non-Human Primates (Nhp) Macaca fascicularis, rat (Sprague Dawley), and mouse (C57BL6/C), supported by proteasome inhibition and p97 RNA silencing data. Importantly, the p97-PROTAC mechanism operates independently of ubiquitination, demonstrated through degradation of clinically relevant proteins such as alpha-synuclein using a camelid nanobody (NbSyn87).

   Major comments:

   * Anti-GFP Nanobody clarification: Details about the original anti-GFP nanobody are unclear, which makes reproducing the current work a challenge for outside labs.

   o 20. Fulcher LJ, Macartney T, Bozatzi P, Hornberger A, Rojas-Fernandez A, Sapkota GP. An affinity-directed protein missile system for targeted proteolysis. Open Biol. Oct 2016;6(10)doi:10.1098/rsob.160255

   o I assume that the anti-GFP nanobody is aGFP from supplementary figure #2 in the Fulcher manuscript but is unclear as they also have used anti-GFP nanobody aGFP16.

   * Amino acids from FAF1-UBX domain: Further clarity is needed regarding the amino acid details from the FAF1-UBX domain, which may have been disclosed in a patent application but should be explicitly outlined in the methods section.

   We appreciate your comment regarding the need for further clarity on the amino acid details from the FAF1-UBX domain. To address this, we have added a supplementary figure which includes a table outlining the amino acid sequences of our construct and the FAF1-UBX domain. This supplementary figure provides a detailed representation of the amino acid sequences. We hope this addition meets your requirements and provides the necessary information for a comprehensive understanding of our work.

   __* Degradation of Proteins of Clinical Interest: The data presented is not convincing enough to support the stated claims that the PROTAC is clearing aggregated mutant HTT. In Figure 5, there is an abundance of GFP-HTT Q74 puncta. While the western blot data suggests a reduction of soluble GFP-HTT-Q74 protein levels, it does not account for aggregated HTT. Aggregated HTT does not efficiently enter the separating gel during electrophoresis. To make these claims the authors need to 1. Show the level of mHTT Q74 aggregation in the empty control groups so that a comparison can be visually made between empty control groups and UBX-Nb(GFP) treated groups. A similar comparison would be useful with the GFP-HTT Q23 treated cells as well. __

   * Visualization of Aggregated Proteins: The continued visibility of puncta raises doubts about the system's efficacy in degrading aggregated proteins. Including comparisons between untreated and treated cells for all test systems would strengthen the argument. It would be useful to show a comparison between the untreated controls and UBX-Nb (GFP) treated cells for all the test systems shown.

   *We acknowledge that the data presented in Figure 5 may not be sufficient to support the claim that the PROTAC is clearing aggregated mutant HTT. The western blot data suggests a reduction in soluble GFP-HTT-Q74 protein levels, but it does not account for aggregated HTT, which does not efficiently enter the separating gel during electrophoresis. We agree that more experiments will need to be performed to evaluate the impact of the p97 PROTAC on the direct turnover of the aggregates once those are form. *

   Minor comments:

   * The In-text citations should be placed outside of the sentence. Example: The ubiquitin-proteasome system (UPS) regulates protein abundance by specific E3 ubiquitin ligases, which catalyze ubiquitin chain formation on the substrates, inducing their proteasome mediated degradation. 1-4

   * Sentence two in the introduction is missing a period. It is unclear whether sentence three is a heading or part of paragraph one.

   * There are additional formatting issues. It would be easier to read the paper if there was a space between paragraphs. Page numbers would be helpful.

   * Page 2. Missing word. Inclusion body myopathy associated with Paget's disease.

   * Figure 1. D, F, and E. Missing annotation to denote significance.

   * Figure 2G Missing annotation to denote significance.

   * Figure 4. Missing annotation to denote significance for figures 4D, 4F, 4H.

   * Is Figure 4I significantly different or not? In Figure 6, you use ns to denote not significant. This feels like it is an important point that you would want to make that the effect is dependent on p97. When you knock out p97 the degradation capacity of UBX-Nb is lost.

   Response

   These changes are going to be apply

   Reviewer #2 (Significance (Required)):

   * The p97-PROTAC system is an ubiquitin-independent approach to degrade intracellular proteins. This system was able to target proteins for degradation at diverse subcellular locations, integral membrane protein residing at the inner nuclear membrane, chromatin located, and liquid-liquid phase separated compartments. The ability to clear alpha-synuclein builds on previous research suggesting that ubiquitin-independent degradation of alpha-synuclein could be a therapeutic approach to treat synucleinopathies such as Parkinson's Disease. However, the ability of this approach to clear aggregated proteins is not convincing, given the presence of visible aggregates in the treated cells.

   * The investigations with NbSyn87 build upon prior research by Butler et al. (2016), who fused NbSyn87 with the mouse Ornithine decarboxylase (ODC) PEST degron. This fusion strategy not only facilitates the targeting of alpha-synuclein but also harnesses the innate cellular machinery responsible for ubiquitin-independent proteolysis. The current approach demonstrates and alternative mechanism to direct alpha-synuclein (and other proteins) into the proteasome for ubiquitin-independent clearance.

   * At the current state of development, this research is of interest to specialized audience with antibody engineering backgrounds; however, it holds translational potential for clearance of toxic proteins.

   * My research interests is in the development of therapeutics for the treatment of neurodegenerative diseases including Huntington's Disease, Parkinson's Disease, and Alzheimer's Disease.

   Read the original source
3. 

   Review Commons

   Jul 11, 2024

   Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

   Learn more at Review Commons

   ---

   Referee #2

   Evidence, reproducibility and clarity

   Summary:

   The authors have developed a p97-directed proteolysis-targeting chimera (PROTAC) that operates independently of ubiquitin. This system employs a camelid nanobody to selectively recognize target proteins, tethered to p97 through the UBX domain of the p97 adapter FAF1. The anti-GFP nanobody effectively targets various GFP-fusion proteins for degradation via the proteasome, relying on p97 for its mechanism of action. The authors validate the presence of p97 in brain tissues of Non-Human Primates (Nhp) Macaca fascicularis, rat (Sprague Dawley), and mouse (C57BL6/C), supported by proteasome inhibition and p97 RNA silencing data. …

   Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

   Learn more at Review Commons

   ---

   Referee #2

   Evidence, reproducibility and clarity

   Summary:

   The authors have developed a p97-directed proteolysis-targeting chimera (PROTAC) that operates independently of ubiquitin. This system employs a camelid nanobody to selectively recognize target proteins, tethered to p97 through the UBX domain of the p97 adapter FAF1. The anti-GFP nanobody effectively targets various GFP-fusion proteins for degradation via the proteasome, relying on p97 for its mechanism of action. The authors validate the presence of p97 in brain tissues of Non-Human Primates (Nhp) Macaca fascicularis, rat (Sprague Dawley), and mouse (C57BL6/C), supported by proteasome inhibition and p97 RNA silencing data. Importantly, the p97-PROTAC mechanism operates independently of ubiquitination, demonstrated through degradation of clinically relevant proteins such as alpha-synuclein using a camelid nanobody (NbSyn87).

   Major comments:

   • Anti-GFP Nanobody clarification: Details about the original anti-GFP nanobody are unclear, which makes reproducing the current work a challenge for outside labs.
     • 1. Fulcher LJ, Macartney T, Bozatzi P, Hornberger A, Rojas-Fernandez A, Sapkota GP. An affinity-directed protein missile system for targeted proteolysis. Open Biol. Oct 2016;6(10)doi:10.1098/rsob.160255
     • I assume that the anti-GFP nanobody is aGFP from supplementary figure #2 in the Fulcher manuscript but is unclear as they also have used anti-GFP nanobody aGFP16.
   • Amino acids from FAF1-UBX domain: Further clarity is needed regarding the amino acid details from the FAF1-UBX domain, which may have been disclosed in a patent application but should be explicitly outlined in the methods section.
   • Degradation of Proteins of Clinical Interest: The data presented is not convincing enough to support the stated claims that the PROTAC is clearing aggregated mutant HTT. In Figure 5, there is an abundance of GFP-HTT Q74 puncta. While the western blot data suggests a reduction of soluble GFP-HTT-Q74 protein levels, it does not account for aggregated HTT. Aggreggated HTT does not efficiently enter the separating gel during electrophoresis. To make these claims the authors need to 1. Show the level of mHTT Q74 aggregation in the empty control groups so that a comparison can be visually made between empty control groups and UBX-Nb(GFP) treated groups. A similar comparison would be useful with the GFP-HTT Q23 treated cells as well.
   • Visualization of Aggregated Proteins: The continued visibility of puncta raises doubts about the system's efficacy in degrading aggregated proteins. Including comparisons between untreated and treated cells for all test systems would strengthen the argument. It would be useful to show a comparison between the untreated controls and UBX-Nb (GFP) treated cells for all the test systems shown.

   Minor comments:

   • The In-text citations should be placed outside of the sentence. Example: The ubiquitin-proteasome system (UPS) regulates protein abundance by specific E3 ubiquitin ligases, which catalyze ubiquitin chain formation on the substrates, inducing their proteasome mediated degradation. 1-4
   • Sentence two in the introduction is missing a period. It is unclear whether sentence three is a heading or part of paragraph one.
   • There are additional formatting issues. It would be easier to read the paper if there was a space between paragraphs. Page numbers would be helpful.
   • Page 2. Missing word. Inclusion body myopathy associated with Paget's disease.
   • Figure 1. D, F, and E. Missing annotation to denote significance.
   • Figure 2G Missing annotation to denote significance.
   • Figure 4. Missing annotation to denote significance for figures 4D, 4F, 4H.
   • Is Figure 4I significantly different or not? In Figure 6, you use ns to denote not significant. This feels like it is an important point that you would want to make that the effect is dependent on p97. When you knock out p97 the degradation capacity of UBX-Nb is lost.

   Significance

   • The p97-PROTAC system is an ubiquitin-independent approach to degrade intracellular proteins. This system was able to target proteins for degradation at diverse subcellular locations, integral membrane protein residing at the inner nuclear membrane, chromatin located and liquid-liquid phase separated compartments. The ability to clear alpha-synuclein builds on previous research suggesting that ubiquitin-independent degradation of alpha-synuclein could be a therapeutic approach to treat synucleinopathies such as Parkinson's Disease. However, the ability of this approach to clear aggregated proteins is not convincing, given the presence of visible aggregates in the treated cells.
   • The investigations with NbSyn87 build upon prior research by Butler et al. (2016), who fused NbSyn87 with the mouse Ornithine decarboxylase (ODC) PEST degron. This fusion strategy not only facilitates the targeting of alpha-synuclein but also harnesses the innate cellular machinery responsible for ubiquitin-independent proteolysis. The current approach demonstrates and alternative mechanism to direct alpha-synuclein (and other proteins) into the proteasome for ubiquitin-independent clearance.
   • At the current state of development, this research is of interest to specialized audience with antibody engineering backgrounds; however, it holds translational potential for clearance of toxic proteins.
   • My research interests is in the development of therapeutics for the treatment of neurodegenerative diseases including Huntington's Disease, Parkinson's Disease, and Alzheimer's Disease.

   Read the original source
4. 

   Review Commons

   Jul 11, 2024

   Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

   Learn more at Review Commons

   ---

   Referee #1

   Evidence, reproducibility and clarity

   The paper by Salinas-Rebolledo et al. describes a novel PROTAC approach in which the UBX domain of FAF1 is fused to a nanobody that recognizes the target protein. The idea is that the UBX domain will bind the fusion protein to the p97 ATPase, a major ATPase involved in the unfolding of many proteins. The target protein recognized by the UBX-nanobody fusion (UBX-Nb) is then supposed to be unfolded in a ubiquitin-independent manner and subsequently degraded by the proteasome.

   The authors provide evidence that Ubx-Nb, containing a nanobody recognizing GFP, can colocalize with GFP fusion proteins in the nucleus and to liquid-liquid …

   Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

   Learn more at Review Commons

   ---

   Referee #1

   Evidence, reproducibility and clarity

   The paper by Salinas-Rebolledo et al. describes a novel PROTAC approach in which the UBX domain of FAF1 is fused to a nanobody that recognizes the target protein. The idea is that the UBX domain will bind the fusion protein to the p97 ATPase, a major ATPase involved in the unfolding of many proteins. The target protein recognized by the UBX-nanobody fusion (UBX-Nb) is then supposed to be unfolded in a ubiquitin-independent manner and subsequently degraded by the proteasome.

   The authors provide evidence that Ubx-Nb, containing a nanobody recognizing GFP, can colocalize with GFP fusion proteins in the nucleus and to liquid-liquid phase separation structures. Importantly, the fusion can reduce the cellular levels of the target proteins. The authors confirm that degradation triggered by Ubx-Nb is proteasome dependent. Ubx-Nb can also promote the degradation of model proteins that form aggregates relevant to neurodegenerative diseases.

   The major issue with the paper is that it does not provide mechanistic insight into the degradation mechanism. First, the data implicating p97 in degradation are conflicting. On the one hand, siRNA of p97 compromises degradation (although degradation is not completely inhibited; see Figure 4G), but on the other hand, an inhibitor of p97 does not have an effect. The authors have not shown that target proteins are actually unfolded by their artificial adaptor (in vitro experiments would be required). In addition, it would be important to show co-localization in vivo with p97. Thus, the role of p97 is not convincingly established. Another major question is how the unfolded, non-ubiquitinated proteins would be degraded by the 26S proteasome. Is there a ubiquitin ligase required after substrate unfolding?

   Overall, the paper reports some intriguing effects of their designed PROTAC adaptor, but the mechanism by which it functions remains unclear. The findings of the manuscript appears too preliminary in its current version for it to be of value to the community.

   Specific points:

   Fig. 1B: Although emerin is reported to be a nuclear envelope protein, it is not localized to the NE, but throughout the ER, likely because the protein was too highly expressed.

   Fig. 1B: ETV co-localization is not obvious from the figure.

   Fig. 4: The depletion of p97 leads to cell death, so it is unclear whether the siRNA effect is specific.

   Fig. 5C: The colocalization of GFP-HTT Q23 with UBX-Nb(GFP) is not entirely convincing.

   Significance

   Overall, the paper reports some intriguing effects of their designed PROTAC adaptor, but the mechanism by which it functions remains unclear. The findings of the manuscript appears too preliminary in its current version for it to be of value to the community.

   Read the original source
5. 

   Version published to 10.1101/2024.03.08.584142 on bioRxiv

   Mar 9, 2024