ORCID
Joseph Harrison: 0000-0002-2118-6524
Document Type
Article
Publication Title
Cell Reports
Department
Chemistry
ISSN
2211-1247
Volume
12
Issue
9
DOI
10.1016/j.celrep.2015.07.046
First Page
1400
Last Page
1406
Publication Date
9-1-2015
Abstract
The protein stability and chromatin functions of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) are regulated in a cell-cycle-dependent manner. We report a structural characterization of the complex between UHRF1 and the deubiquitinase USP7. The first two UBL domains of USP7 bind to the polybasic region (PBR) of UHRF1, and this interaction is required for the USP7-mediated deubiquitination of UHRF1. Importantly, we find that the USP7-binding site of the UHRF1 PBR overlaps with the region engaging in an intramolecular interaction with the N-terminal tandem Tudor domain (TTD). We show that the USP7-UHRF1 interaction perturbs the TTD-PBR interaction of UHRF1, thereby shifting the conformation of UHRF1 from a TTD-"occluded" state to a state open for multivalent histone binding. Consistently, introduction of a USP7-interaction-defective mutation to UHRF1 significantly reduces its chromatin association. Together, these results link USP7 interaction to the dynamic deubiquitination and chromatin association of UHRF1.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Zhang, Z.,
Rothbart, S. B.,
Allison, D. F.,
Cai, Q.,
Harrison, J. S.,
Li, L.,
Wang, Y.,
Strahl, B. D.,
Wang, G. G.,
&
Song, J.
(2015).
An Allosteric Interaction Links USP7 to Deubiquitination and Chromatin Targeting of UHRF1.
Cell Reports, 12(9), 1400–1406.
DOI: 10.1016/j.celrep.2015.07.046
https://scholarlycommons.pacific.edu/cop-facarticles/575
