Characterization of the Cullin7 E3 ubiquitin ligase — Heterodimerization of cullin substrate receptors as a novel mechanism to regulate cullin E3 ligase activity

2012 ◽  
Vol 24 (1) ◽  
pp. 290-295 ◽  
Author(s):  
Wanpen Ponyeam ◽  
Thilo Hagen
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
E3 Ligase

scholarly journals Heterologous Expression and Molecular and Cellular Characterization of CaPUB1 Encoding a Hot Pepper U-Box E3 Ubiquitin Ligase Homolog

2006 ◽  
Vol 142 (4) ◽  
pp. 1664-1682 ◽  
Author(s):  
Seok Keun Cho ◽  
Hoo Sun Chung ◽  
Moon Young Ryu ◽  
Mi Jin Park ◽  
Myeong Min Lee ◽  
...  
Keyword(s):  
Heterologous Expression ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Hot Pepper

scholarly journals Inhibition of cIAP1 as a strategy for targeting c-MYC–driven oncogenic activity

2018 ◽  
Vol 115 (40) ◽  
pp. E9317-E9324 ◽  
Author(s):  
Haoyan Li ◽  
Yanjia Fang ◽  
Chunyi Niu ◽  
Hengyi Cao ◽  
Ting Mi ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
E3 Ligase ◽  
Pharmacological Agents ◽  
Protein Levels ◽  
Ubiquitin Ligase Activity ◽  
Molecule Inhibitor ◽  
Smac Mimetics ◽  
High Throughput Assay ◽  
In Cells

Protooncogenec-MYC, a master transcription factor, is a major driver of human tumorigenesis. Development of pharmacological agents for inhibiting c-MYC as an anticancer therapy has been a longstanding but elusive goal in the cancer field. E3 ubiquitin ligase cIAP1 has been shown to mediate the activation of c-MYC by destabilizing MAD1, a key antagonist of c-MYC. Here we developed a high-throughput assay for cIAP1 ubiquitination and identified D19, a small-molecule inhibitor of E3 ligase activity of cIAP1. We show that D19 binds to the RING domain of cIAP1 and inhibits the E3 ligase activity of cIAP1 by interfering with the dynamics of its interaction with E2. Blocking cIAP1 with D19 antagonizes c-MYC by stabilizing MAD1 protein in cells. Furthermore, we show that D19 and an improved analog (D19-14) promote c-MYC degradation and inhibit the oncogenic function of c-MYC in cells and xenograft animal models. In contrast, we show that activating E3 ubiquitin ligase activity of cIAP1 by Smac mimetics destabilizes MAD1, the antagonist of MYC, and increases the protein levels of c-MYC. Our study provides an interesting example using chemical biological approaches for determining distinct biological consequences from inhibiting vs. activating an E3 ubiquitin ligase and suggests a potential broad therapeutic strategy for targeting c-MYC in cancer treatment by pharmacologically modulating cIAP1 E3 ligase activity.

scholarly journals The sterol-responsive RNF145 E3 ubiquitin ligase mediates the degradation of HMG-CoA reductase together with gp78 and Hrd1

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sam A Menzies ◽  
Norbert Volkmar ◽  
Dick JH van den Boomen ◽  
Richard T Timms ◽  
Anna S Dickson ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Critical Role ◽  
E3 Ubiquitin Ligase ◽  
E3 Ligase ◽  
Editorial Note ◽  
Hmg Coa Reductase ◽  
Genome Wide ◽  
Cholesterol Biosynthetic Pathway ◽  
Coa Reductase ◽  
Rate Limiting

Mammalian HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the cholesterol biosynthetic pathway and the therapeutic target of statins, is post-transcriptionally regulated by sterol-accelerated degradation. Under cholesterol-replete conditions, HMGCR is ubiquitinated and degraded, but the identity of the E3 ubiquitin ligase(s) responsible for mammalian HMGCR turnover remains controversial. Using systematic, unbiased CRISPR/Cas9 genome-wide screens with a sterol-sensitive endogenous HMGCR reporter, we comprehensively map the E3 ligase landscape required for sterol-accelerated HMGCR degradation. We find that RNF145 and gp78 independently co-ordinate HMGCR ubiquitination and degradation. RNF145, a sterol-responsive ER-resident E3 ligase, is unstable but accumulates following sterol depletion. Sterol addition triggers RNF145 recruitment to HMGCR via Insigs, promoting HMGCR ubiquitination and proteasome-mediated degradation. In the absence of both RNF145 and gp78, Hrd1, a third UBE2G2-dependent E3 ligase, partially regulates HMGCR activity. Our findings reveal a critical role for the sterol-responsive RNF145 in HMGCR regulation and elucidate the complexity of sterol-accelerated HMGCR degradation.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

E3 ubiquitin ligase tripartite motif 7 positively regulates the TLR4-mediated immune response via its E3 ligase domain in macrophages

2019 ◽  
Vol 109 ◽  
pp. 126-133 ◽  
Author(s):  
Mingfeng Lu ◽  
Xuhui Zhu ◽  
Zhizhou Yang ◽  
Wei Zhang ◽  
Zhaorui Sun ◽  
...  
Keyword(s):  
Immune Response ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
E3 Ligase ◽  
Tripartite Motif

scholarly journals Wnt regulation: exploring Axin-Disheveled interactions and defining mechanisms by which the SCF E3 ubiquitin ligase is recruited to the destruction complex

2020 ◽  
Vol 31 (10) ◽  
pp. 992-1014 ◽  
Author(s):  
Kristina N. Schaefer ◽  
Mira I. Pronobis ◽  
Clara E. Williams ◽  
Shiping Zhang ◽  
Lauren Bauer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Development ◽  
Wnt Signaling ◽  
Ubiquitin Ligase ◽  
Human Cancer ◽  
E3 Ubiquitin Ligase ◽  
E3 Ligase ◽  
Adult Stem Cell ◽  
Cell Homeostasis ◽  
Test Models

Wnt signaling plays key roles in embryonic development and adult stem cell homeostasis and is altered in human cancer. We explore β-catenin transfer from the destruction complex to the E3 ligase, and test models suggesting Dishevelled and APC2 compete for association with Axin.

Cloning and characterization of mouse cullin4B/E3 ubiquitin ligase

2005 ◽  
Vol 30 (3) ◽  
pp. 329-337 ◽  
Author(s):  
Rachana Tripathi ◽  
K. Seetharama Sastry ◽  
Satya Keerthi Kota ◽  
Usha K. Srinivas
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase

scholarly journals Characterization of the Interaction of Full-Length HIV-1 Vif Protein with its Key Regulator CBFβ and CRL5 E3 Ubiquitin Ligase Components

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e33495 ◽  
Author(s):  
Xiaohong Zhou ◽  
Sean L. Evans ◽  
Xue Han ◽  
Yayan Liu ◽  
Xiao-Fang Yu
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Full Length ◽  
Vif Protein ◽  
Hiv 1

scholarly journals The sterol-responsive RNF145 E3 ubiquitin ligase mediates the degradation of HMG-CoA reductase together with gp78 and Hrd1

2018 ◽  
Author(s):  
Sam A. Menzies ◽  
Norbert Volkmar ◽  
Dick J. van den Boomen ◽  
Richard T. Timms ◽  
Anna S. Dickson ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Critical Role ◽  
E3 Ubiquitin Ligase ◽  
E3 Ligase ◽  
Hmg Coa Reductase ◽  
Accelerated Degradation ◽  
Genome Wide ◽  
Cholesterol Biosynthetic Pathway ◽  
Coa Reductase ◽  
Rate Limiting

ABSTRACTHMG-CoA reductase (HMGCR), the rate-limiting enzyme of the cholesterol biosynthetic pathway and the therapeutic target of statins, is post-transcriptionally regulated by sterol-accelerated degradation. Under cholesterol-replete conditions, HMGCR is ubiquitinated and degraded, but the identity of the E3 ubiquitin ligase(s) responsible for mammalian HMGCR turnover remains controversial. Using systematic, unbiased CRISPR/Cas9 genome-wide screens with a sterol-sensitive endogenous HMGCR reporter, we comprehensively map the E3 ligase landscape required for sterol-accelerated HMGCR degradation. We find that RNF145 and gp78, independently co-ordinate HMGCR ubiquitination and degradation. RNF145, a sterol-responsive ER-resident E3 ligase, is unstable but accumulates following sterol depletion. Sterol addition triggers RNF145 recruitment to HMGCR and Insig-1, promoting HMGCR ubiquitination and proteasome-mediated degradation. In the absence of both RNF145 and gp78, Hrd1, a third UBE2G2-dependent ligase partially regulates HMGCR activity. Our findings reveal a critical role for the sterol-responsive RNF145 in HMGCR regulation and elucidate the complexity of sterol-accelerated HMGCR degradation.

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