Abstract

We have moved all aspects of this umbrella project forward during 2013. We discovered that C-terminal domains within ATPase proteins that dock against the proteasome's core particle undergo dynamic exchange between an expected 4-helix bundle and a partially unfolded state. We provided evidence that this exchange is important for interactions with chaperones involved in proteasome assembly. In unpublished work, we have moved forward the resolution of the 3D structures for multiple protein complexes, including a new ubiquitin binding motif. During 2013, we also characterized a small molecule that restricts proliferation of multiple cancer cell lines. This work was collaborative with the Roden lab at Johns Hopkins University and led to the characterization of ubiquitin receptor Rpn13 as a potential target for certain cancer types.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011490-02
Application #
8938154
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Calabrese, David R; Chen, Xiang; Leon, Elena C et al. (2018) Chemical and structural studies provide a mechanistic basis for recognition of the MYC G-quadruplex. Nat Commun 9:4229
Lu, Xiuxiu; Nowicka, Urszula; Sridharan, Vinidhra et al. (2017) Structure of the Rpn13-Rpn2 complex provides insights for Rpn13 and Uch37 as anticancer targets. Nat Commun 8:15540
Chen, Xiang; Randles, Leah; Shi, Ke et al. (2016) Structures of Rpn1 T1:Rad23 and hRpn13:hPLIC2 Reveal Distinct Binding Mechanisms between Substrate Receptors and Shuttle Factors of the Proteasome. Structure 24:1257-1270
Rao, Timsi; Gao, Rui; Takada, Saeko et al. (2016) Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage. Nucleic Acids Res 44:10201-10215
Finley, Daniel; Chen, Xiang; Walters, Kylie J (2016) Gates, Channels, and Switches: Elements of the Proteasome Machine. Trends Biochem Sci 41:77-93
Randles, Leah; Anchoori, Ravi K; Roden, Richard B S et al. (2016) The Proteasome Ubiquitin Receptor hRpn13 and Its Interacting Deubiquitinating Enzyme Uch37 Are Required for Proper Cell Cycle Progression. J Biol Chem 291:8773-83
Shi, Yuan; Chen, Xiang; Elsasser, Suzanne et al. (2016) Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome. Science 351:
Chen, Xiang; Walters, Kylie J (2016) (1)H, (15)N, (13)C resonance assignments for Saccharomyces cerevisiae Rad23 UBL domain. Biomol NMR Assign 10:291-5
Nowicka, Urszula; Hoffman, Morgan; Randles, Leah et al. (2016) Mycobacterium tuberculosis copper-regulated protein SocB is an intrinsically disordered protein that folds upon interaction with a synthetic phospholipid bilayer. Proteins 84:193-200
Yu, Clinton; Yang, Yingying; Wang, Xiaorong et al. (2016) Characterization of Dynamic UbR-Proteasome Subcomplexes by In vivo Cross-linking (X) Assisted Bimolecular Tandem Affinity Purification (XBAP) and Label-free Quantitation. Mol Cell Proteomics 15:2279-92

Showing the most recent 10 out of 18 publications