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BioAssay: AID 485343

Summary of small molecule inhibitors of UBC13 Polyubiquitin

Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are a family of adapter proteins that bind an unusual ubiquitin-conjugating enzyme, Ubc13, which produces polyubiquitin chains linked at lysine 63 of ubiquitin. These lysine 63-linked ubiquitin polymers trigger changes in protein activity. Ubiquitination by Ubc13 of TRAFs and the various protein kinases to which TRAFs bind is recognized as more ..
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AID: 485343
Data Source: Burnham Center for Chemical Genomics (SBCCG-A443-UBC13-Summary-Assay)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2010-10-04
Modify Date: 2011-04-25
Target
Depositor Specified Assays
Show more
AIDNameTypeComment
485273uHTS identification of UBC13 Polyubiquitin Inhibitors via a TR-FRET AssayscreeningPrimary Screen
504680SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Caspase-3 counterscreenconfirmatory
504685SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreenconfirmatory
504687SAR analysis of small molecule UBC13 Polyubiquitin Inhibitors via a TR-FRET Assayconfirmatory
602206SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreen - Set 3confirmatory
602205SAR analysis of small molecule UBC13 Polyubiquitin Inhibitors via a TR-FRET Assay - Set 3confirmatory
588375SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Caspase-3 counterscreen - Set 2confirmatory
602404SAR analysis of small molecule UBC13 Polyubiquitin Inhibitors via a TR-FRET Assay - Set 4confirmatory
588376SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreen - Set 2confirmatory
602401SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Caspase-3 counterscreen - Set 4confirmatory
493155Dose Response confirmation of uHTS for the identification of UBC13 Polyubiquitin Inhibitors via a TR-FRET Assayconfirmatory
602207SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Caspase-3 counterscreen - Set 3confirmatory
602400SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreen - Set 4confirmatory
588390SAR analysis of small molecule UBC13 Polyubiquitin Inhibitors via a TR-FRET Assay - Set 2confirmatory
504689Dose Response confirmation of UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreenconfirmatory
488856Single concentration confirmation of UBC13 Polyubiquitin Inhibitors using a Caspase-3 counter screenscreening
488859Single concentration confirmation of uHTS for the identification of UBC13 Polyubiquitin Inhibitors via a TR-FRET Assayscreening
493182Dose Response confirmation of uHTS for the identification of UBC13 Polyubiquitin Inhibitors via a TR-FRET Assay reconfirmconfirmatory
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1R03 MH085677-01
Assay Provider: Dr. John C. Reed, Sanford-Burnham Medical Research Institute, San Diego CA

Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are a family of adapter proteins that bind an unusual ubiquitin-conjugating enzyme, Ubc13, which produces polyubiquitin chains linked at lysine 63 of ubiquitin. These lysine 63-linked ubiquitin polymers trigger changes in protein activity. Ubiquitination by Ubc13 of TRAFs and the various protein kinases to which TRAFs bind is recognized as a critical step in signaling by TNFRs, TLRs, NLRs, and T-cell and B-cell antigen receptors (TCR/BCR) during innate and acquired immune responses. Since aberrant signaling by these receptor systems is linked to a wide variety of autoimmune, inflammatory, and infectious diseases; compounds that neutralize Ubc13 may prove useful as a novel type of immunosuppressive or anti-inflammatory agent.

REFERENCES
1. Fukushima, T., Matsuzawa, S., Kress, C. L., Bruey, J. M., Krajewska, M., Lefebvre, S., Zapata, J. M., Ronai, Z., and Reed, J.C. (2007) Proc Natl Acad Sci USA 104(15), 6371-6376 (PMC1851032)
2. Yamamoto, M., Okamoto, T., Takeda, K., Sato, S., Sanjo, H., Uematsu, S., Saitoh, T., Yamamoto, N., Sakurai, H., Ishii, K. J., Yamaoka, S., Kawai, T., Matsuura, Y., Takeuchi, O., and Akira, S. (2006) Nat Immunol 7, 962-970
3. Yamamoto, M., Sato, S., Saitoh, T., Sakurai, H., Uematsu, S., Kawai, T., Ishii, K. J., Takeuchi, O., and Akira, S. (2006) J Immunol 177, 7520-7524
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8. Wooff, J., Pastushok, L., Hanna, M., Fu, Y., and Xiao, W. (2004) FEBS Lett 566, 229-233
9. Wu, H., and Arron, J. R. (2003) Bioessays 25, 1096-1105
10. McKenna, S., Hu, J., Moraes, T., Xiao, W., Ellison, M. J., and Spyracopoulos, L. (2003) Biochemistry 42, 7922-7930
11. Hau, D. D., Lewis, M. J., Saltibus, L. F., Pastushok, L., Xiao, W., and Spyracopoulos, L. (2006) Biochemistry 45, 9866-9877
Protocol
Please see pertinent AIDs: 485273, 504680, 504685, 504687
Comment
Probe molecules are defined as the positives of this assay and assigned a score of 100. Testing has not progressed to the point where a probe molecule has been identified.
Additional Information
Grant Number: 1R03 MH085677-01

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