Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly

Brown, Nicholas G.; Watson, Edmond R.; Weissmann, Florian; Jarvis, Marc A.; VanderLinden, Ryan; Grace, Christy R. R.; Frye, Jeremiah J.; Qiao, Renping; Dube, Prakash; Petzold, Georg; Cho, Shein Ei; Alsharif, Omar; Bao, Ju; Davidson, Iain F.; Zheng, Jie J.; Nourse, Amanda; Kurinov, Igor; Peters, Jan-Michael; Stark, Holger; Schulman, Brenda A.

doi:10.1016/j.molcel.2014.09.009

Title: Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly

Full Record
Other Related Research

Abstract

Polyubiquitination by E2 and E3 enzymes is a predominant mechanism regulating protein function. Some RING E3s, including anaphase-promoting complex/cyclosome (APC), catalyze polyubiquitination by sequential reactions with two different E2s. An initiating E2 ligates ubiquitin to an E3-bound substrate. Another E2 grows a polyubiquitin chain on the ubiquitin-primed substrate through poorly defined mechanisms. Here in this paper we show that human APC’s RING domain is repurposed for dual functions in polyubiquitination. The canonical RING surface activates an initiating E2-ubiquitin intermediate for substrate modification. However, APC engages and activates its specialized ubiquitin chain-elongating E2 UBE2S in ways that differ from current paradigms. During chain assembly, a distinct APC11 RING surface helps deliver a substrate-linked ubiquitin to accept another ubiquitin from UBE2S. Our data define mechanisms of APC/UBE2S-mediated polyubiquitination, reveal diverse functions of RING E3s and E2s, and provide a framework for understanding distinctive RING E3 features specifying ubiquitin chain elongation.

Publication Date:: Wed Oct 01 00:00:00 EDT 2014

Research Org.:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:: USDOE Office of Science (SC); Jane Coffin Childs Foundation; German Research Foundation (DFG); Austrian Research Fund

OSTI Identifier:: 1227558

Alternate Identifier(s):: OSTI ID: 1163386

Grant/Contract Number:: AC02-06CH11357; 227764

Resource Type:: Published Article

Journal Name:: Molecular Cell

Additional Journal Information:: Journal Name: Molecular Cell Journal Volume: 56 Journal Issue: 2; Journal ID: ISSN 1097-2765

Publisher:: Elsevier

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES

Citation Formats


                    Brown, Nicholas G., Watson, Edmond R., Weissmann, Florian, Jarvis, Marc A., VanderLinden, Ryan, Grace, Christy R. R., Frye, Jeremiah J., Qiao, Renping, Dube, Prakash, Petzold, Georg, Cho, Shein Ei, Alsharif, Omar, Bao, Ju, Davidson, Iain F., Zheng, Jie J., Nourse, Amanda, Kurinov, Igor, Peters, Jan-Michael, Stark, Holger, and Schulman, Brenda A. Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly.  United States: N. p., 2014. 
Web.  doi:10.1016/j.molcel.2014.09.009.

Copy to clipboard


                    Brown, Nicholas G., Watson, Edmond R., Weissmann, Florian, Jarvis, Marc A., VanderLinden, Ryan, Grace, Christy R. R., Frye, Jeremiah J., Qiao, Renping, Dube, Prakash, Petzold, Georg, Cho, Shein Ei, Alsharif, Omar, Bao, Ju, Davidson, Iain F., Zheng, Jie J., Nourse, Amanda, Kurinov, Igor, Peters, Jan-Michael, Stark, Holger, & Schulman, Brenda A. Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly.  United States.  https://doi.org/10.1016/j.molcel.2014.09.009

Copy to clipboard


                    Brown, Nicholas G., Watson, Edmond R., Weissmann, Florian, Jarvis, Marc A., VanderLinden, Ryan, Grace, Christy R. R., Frye, Jeremiah J., Qiao, Renping, Dube, Prakash, Petzold, Georg, Cho, Shein Ei, Alsharif, Omar, Bao, Ju, Davidson, Iain F., Zheng, Jie J., Nourse, Amanda, Kurinov, Igor, Peters, Jan-Michael, Stark, Holger, and Schulman, Brenda A. Wed .  
"Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly".  United States.  https://doi.org/10.1016/j.molcel.2014.09.009.

Copy to clipboard


                    
@article{osti_1227558,

  title        = {Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly},

  author       = {Brown, Nicholas G. and Watson, Edmond R. and Weissmann, Florian and Jarvis, Marc A. and VanderLinden, Ryan and Grace, Christy R. R. and Frye, Jeremiah J. and Qiao, Renping and Dube, Prakash and Petzold, Georg and Cho, Shein Ei and Alsharif, Omar and Bao, Ju and Davidson, Iain F. and Zheng, Jie J. and Nourse, Amanda and Kurinov, Igor and Peters, Jan-Michael and Stark, Holger and Schulman, Brenda A.},

  abstractNote = {Polyubiquitination by E2 and E3 enzymes is a predominant mechanism regulating protein function. Some RING E3s, including anaphase-promoting complex/cyclosome (APC), catalyze polyubiquitination by sequential reactions with two different E2s. An initiating E2 ligates ubiquitin to an E3-bound substrate. Another E2 grows a polyubiquitin chain on the ubiquitin-primed substrate through poorly defined mechanisms. Here in this paper we show that human APC’s RING domain is repurposed for dual functions in polyubiquitination. The canonical RING surface activates an initiating E2-ubiquitin intermediate for substrate modification. However, APC engages and activates its specialized ubiquitin chain-elongating E2 UBE2S in ways that differ from current paradigms. During chain assembly, a distinct APC11 RING surface helps deliver a substrate-linked ubiquitin to accept another ubiquitin from UBE2S. Our data define mechanisms of APC/UBE2S-mediated polyubiquitination, reveal diverse functions of RING E3s and E2s, and provide a framework for understanding distinctive RING E3 features specifying ubiquitin chain elongation.},

  doi          = {10.1016/j.molcel.2014.09.009},

  journal      = {Molecular Cell},

  number       = 2,

  volume       = 56,

  place        = {United States},

  year         = {Wed Oct 01 00:00:00 EDT 2014},

  month        = {Wed Oct 01 00:00:00 EDT 2014}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Publisher's Version of Record
https://doi.org/10.1016/j.molcel.2014.09.009

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 78 works

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Similar Records in DOE PAGES and OSTI.GOV collections:

RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex

Journal Article Brown, Nicholas G. ; VanderLinden, Ryan ; Watson, Edmond R. ; ... - Proceedings of the National Academy of Sciences of the United States of America

For many E3 ligases, a mobile RING (Really Interesting New Gene) domain stimulates ubiquitin (Ub) transfer from a thioester-linked E2~Ub intermediate to a lysine on a remotely bound disordered substrate. One such E3 is the gigantic, multisubunit 1.2-MDa anaphase-promoting complex/cyclosome (APC), which controls cell division by ubiquitinating cell cycle regulators to drive their timely degradation. Intrinsically disordered substrates are typically recruited via their KEN-box, D-box, and/or other motifs binding to APC and a coactivator such as CDH1. On the opposite side of the APC, the dynamic catalytic core contains the cullin-like subunit APC2 and its RING partner APC11, which collaboratesmore »« less
Cited by 68
https://doi.org/10.1073/pnas.1504161112

Full Text Available
Protein engineering of a ubiquitin-variant inhibitor of APC/C identifies a cryptic K48 ubiquitin chain binding site

Journal Article Watson, Edmond R. ; Grace, Christy R. R. ; Zhang, Wei ; ... - Proceedings of the National Academy of Sciences of the United States of America

Ubiquitin (Ub)-mediated proteolysis is a fundamental mechanism used by eukaryotic cells to maintain homeostasis and protein quality, and to control timing in biological processes. Two essential aspects of Ub regulation are conjugation through E1-E2-E3 enzymatic cascades and recognition by Ub-binding domains. An emerging theme in the Ub field is that these 2 properties are often amalgamated in conjugation enzymes. In addition to covalent thioester linkage to Ub’s C terminus for Ub transfer reactions, conjugation enzymes often bind noncovalently and weakly to Ub at “exosites.” However, identification of such sites is typically empirical and particularly challenging in large molecular machines. Inmore »« less
Cited by 15
https://doi.org/10.1073/pnas.1902889116

Full Text Available
Structure And Function of the Yeast U-Box-Containing Ubiquitin Ligase Ufd2p

Journal Article Tu, D ; Li, W ; Ye, Y ; ... - Proc. Nat. Acad. Sci. 104:15599,2007

Proteins conjugated by Lys-48-linked polyubiquitin chains are preferred substrates of the eukaryotic proteasome. Polyubiquitination requires an activating enzyme (E1), a conjugating enzyme (E2), and a ligase (E3). Occasionally, these enzymes only assemble short ubiquitin oligomers, and their extension to full length involves a ubiquitin elongating factor termed E4. Ufd2p, as the first E4 identified to date, is involved in the degradation of misfolded proteins of the endoplasmic reticulum and of a ubiquitin-{beta}-GAL fusion substrate in Saccharomyces cerevisiae. The mechanism of action of Ufd2p is unknown. Here we describe the crystal structure of the full-length yeast Ufd2p protein. Ufd2p has anmore »« less
Structure of an APC3–APC16 Complex: Insights into Assembly of the Anaphase-Promoting Complex/Cyclosome

Journal Article Yamaguchi, Masaya ; Yu, Shanshan ; Qiao, Renping ; ... - Journal of Molecular Biology

The anaphase-promoting complex/cyclosome (APC/C) is a massive E3 ligase that controls mitosis by catalyzing ubiquitination of key cell cycle regulatory proteins. The APC/C assembly contains two subcomplexes: the “Platform” centers around a cullin-RING-like E3 ligase catalytic core; the “Arc Lamp” is a hub that mediates transient association with regulators and ubiquitination substrates. The Arc Lamp contains the small subunits APC16, CDC26, and APC13, and tetratricopeptide repeat (TPR) proteins (APC7, APC3, APC6, and APC8) that homodimerize and stack with quasi-2-fold symmetry. Within the APC/C complex, APC3 serves as center for regulation. APC3's TPR motifs recruit substrate-binding coactivators, CDC20 and CDH1, viamore »« less
Cited by 28
https://doi.org/10.1016/j.jmb.2014.11.020

Full Text Available
UBE2S associated with OSCC proliferation by promotion of P21 degradation via the ubiquitin-proteasome system

Journal Article Yoshimura, Shusaku ; Kasamatsu, Atsushi ; Nakashima, Dai ; ... - Biochemical and Biophysical Research Communications

Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitin-proteasome system, is highly expressed in several types of cancers; however, its roles in oral squamous cell carcinoma (OSCC) have not yet been well elucidated. The purpose of this study was to clarify the functional activities of UBE2S in OSCCs. We analyzed the expression levels of UBE2S in nine OSCC cell lines and primary OSCC tissues by quantitative reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry (IHC). The correlations between UBE2S expression and clinical classifications of OSCCs were analyzed using the IHC scoring system. We also used UBE2S knockdownmore »« less
https://doi.org/10.1016/J.BBRC.2017.02.138

Similar Records