Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation.

Cell | 2016

Hundreds of human cullin-RING E3 ligases (CRLs) modify thousands of proteins with ubiquitin (UB) to achieve vast regulation. Current dogma posits that CRLs first catalyze UB transfer from an E2 to their client substrates and subsequent polyubiquitylation from various linkage-specific E2s. We report an alternative E3-E3 tagging cascade: many cellular NEDD8-modified CRLs associate with a mechanistically distinct thioester-forming RBR-type E3, ARIH1, and rely on ARIH1 to directly add the first UB and, in some cases, multiple additional individual monoubiquitin modifications onto CRL client substrates. Our data define ARIH1 as a component of the human CRL system, demonstrate that ARIH1 can efficiently and specifically mediate monoubiquitylation of several CRL substrates, and establish principles for how two distinctive E3s can reciprocally control each other for simultaneous and joint regulation of substrate ubiquitylation. These studies have broad implications for CRL-dependent proteostasis and mechanisms of E3-mediated UB ligation.

Pubmed ID: 27565346 RIS Download

Additional research tools detected in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R37 NS083524
  • Agency: European Research Council, International
    Id: 281699
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM069530
  • Agency: NIDDK NIH HHS, United States
    Id: K01 DK098285
  • Agency: NIA NIH HHS, United States
    Id: R01 AG011085
  • Agency: NCI NIH HHS, United States
    Id: P30 CA021765
  • Agency: Howard Hughes Medical Institute, United States

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Cry2 Antibody (antibody)

RRID:AB_10554665

This unknown targets Cry2

View all literature mentions

Cullin 2 Polyclonal Antibody (antibody)

RRID:AB_2533898

This unknown targets Cullin 2

View all literature mentions

Phospho-NF-κB p65 (Ser536) (93H1) Rabbit mAb (antibody)

RRID:AB_331284

This monoclonal targets NF-KappaB p65, phospho (Ser536)

View all literature mentions

Cry1 Antibody (antibody)

RRID:AB_10555376

This unknown targets Cry1

View all literature mentions

Anti-α-Tubulin antibody (antibody)

RRID:AB_477593

This monoclonal targets α-Tubulin

View all literature mentions

ARIH1 antibody (antibody)

RRID:AB_304129

This polyclonal targets ARIH1 antibody

View all literature mentions

KLHL12 Monoclonal Antibody (2G2) (antibody)

RRID:AB_11004907

This monoclonal targets KLHL12

View all literature mentions

Rabbit Anti-Bovine Deoxyribonuclease I (DNASE1) Polyclonal, Unconjugated (antibody)

RRID:AB_1054763

This polyclonal targets Bovine Deoxyribonuclease I (DNASE1)

View all literature mentions

Skp2 (L70) Antibody (antibody)

RRID:AB_2187641

This polyclonal targets Skp2

View all literature mentions

Skp1 Antibody (antibody)

RRID:AB_2270271

This unknown targets Skp1

View all literature mentions

Human/Mouse/Rat HIF-1 alpha MAb (Clone 241809) (antibody)

RRID:AB_2116983

This monoclonal targets HIF-1 alpha, aa 575-826

View all literature mentions

Anti-GFP (antibody)

RRID:AB_390913

This monoclonal targets GFP

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

Bioconductor (software resource)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Flp-In-T-REx-293 (cell line)

RRID:CVCL_U427

Cell line Flp-In-T-REx-293 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

U2OS (cell line)

RRID:CVCL_0042

Cell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Cry2 Antibody (antibody)

RRID:AB_10554665

This unknown targets Cry2

View all literature mentions

Bioconductor (software resource)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

Cullin 2 Polyclonal Antibody (antibody)

RRID:AB_2533898

This unknown targets Cullin 2

View all literature mentions

Phospho-NF-κB p65 (Ser536) (93H1) Rabbit mAb (antibody)

RRID:AB_331284

This monoclonal targets NF-KappaB p65, phospho (Ser536)

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

Bioconductor (software resource)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

View all literature mentions

U2OS (cell line)

RRID:CVCL_0042

Cell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Cullin 2 Polyclonal Antibody (antibody)

RRID:AB_2533898

This unknown targets Cullin 2

View all literature mentions

Cry2 Antibody (antibody)

RRID:AB_10554665

This unknown targets Cry2

View all literature mentions