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
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 unknown targets Cullin 2
View all literature mentionsThis monoclonal targets IkappaB-alpha
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Cyclin E1
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis monoclonal targets Cdkn1b
View all literature mentionsThis unknown targets NEDD8
View all literature mentionsThis polyclonal targets ARIH1 antibody
View all literature mentionsThis monoclonal targets HIF-1α
View all literature mentionsThis monoclonal targets Proliferating Cell Nuclear Antigen
View all literature mentionsThis monoclonal targets Sec31A
View all literature mentionsThis monoclonal targets KLHL12
View all literature mentionsThis polyclonal targets Bovine Deoxyribonuclease I (DNASE1)
View all literature mentionsThis polyclonal targets CUL 1
View all literature mentionsThis polyclonal targets Skp2
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis monoclonal targets HIF-1 alpha, aa 575-826
View all literature mentionsSoftware 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 mentionsSoftware 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 mentionsStatistical 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 mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Flp-In-T-REx-293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsSoftware 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 mentionsSoftware 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 mentionsThis unknown targets Cullin 2
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsSoftware 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 mentionsSoftware 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 mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets IkappaB-alpha
View all literature mentionsThis unknown targets Cullin 2
View all literature mentions