538 Id1 enhances RING1b E3 ubiquitin ligase activity through the Mel-18/Bmi-1 polycomb group complex

2010 ◽  
Vol 8 (7) ◽  
pp. 171
Author(s):  
J. Lee ◽  
T. Qian ◽  
J. Park ◽  
H. Kim ◽  
G. Kong
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Polycomb Group ◽  
Ubiquitin Ligase Activity

scholarly journals Id1 enhances RING1b E3 ubiquitin ligase activity through the Mel-18/Bmi-1 polycomb group complex

Oncogene ◽  
2010 ◽  
Vol 29 (43) ◽  
pp. 5818-5827 ◽  
Author(s):  
T Qian ◽  
J-Y Lee ◽  
J-H Park ◽  
H-J Kim ◽  
G Kong
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Polycomb Group ◽  
Ubiquitin Ligase Activity

Post-translational regulation of FLC is mediated by an E3 ubiquitin ligase activity of SINAT5 in Arabidopsis

Plant Science ◽  
2007 ◽  
Vol 173 (2) ◽  
pp. 269-275 ◽  
Author(s):  
Bong Soo Park ◽  
Wan Gyu Sang ◽  
Song Yion Yeu ◽  
Yang Do Choi ◽  
Nam-Chon Paek ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Translational Regulation ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligase Activity

Functions of RMR proteins in intracellular trafficking in the moss "Physcomitrium patens" Mitten (previously "Physcomitrella patens")

2021 ◽  
Author(s):  
◽  
Carla Coppola
Keyword(s):  
Ubiquitin Ligase ◽  
Physcomitrella Patens ◽  
Fluorescent Protein ◽  
Storage Proteins ◽  
Higher Plants ◽  
E3 Ubiquitin Ligase ◽  
E3 Ligases ◽  
Ubiquitin Ligase Activity ◽  
Vacuolar Transport

In this study, I focused on a new family of receptors, called RMRs (Receptor-like Membrane RING-H2) and I tried to investigate their role in the moss Physcomitrium patens Mitten (previously Physcomitrella patens). There is some evidence that in Angiosperms, RMRs are vacuolar receptors for the neutral/storage vacuole that is a compartment where storage proteins and metabolites are accumulated during seeds development or in somatic tissues. It is distinguished from lytic vacuole which has the same functions as animal lysosomes. The five PpRMR genes have been knocked-out, yielding viable material without visible phenotype (Ayachi, 2012). A trafficking phenotype was described by Fahr (2017) who generated the construct Citrine-Cardosin (Ci-Card) composed of the fluorescent protein Citrine fused to the C-terminal vacuolar sorting determinant (ctVSD) from cardosin A (cardosin is addressed to the vacuole in higher plants —Pereira et al., 2013). The fusion protein was delivered to the central vacuole of PpWT but mistargeted in PpRMR-KO lines, indicating that the targeting of this protein to the vacuole depends on PpRMRs. The introduction of this thesis presents the plant endomembrane system, with particular attention to vacuolar transport and ubiquitylation. In the second chapter, I show the techniques used to attempt to detect PpRMRs by Western Blot: our failure may be due to a rapid degradation of these proteins, which could prevent their detection. In the third chapter, I focused on PpRMR2 involvement in ubiquitylation. We hypothesize that PpRMRs are E3 ligases because they are members of the PA-TM-RING protein family. Most of these proteins have an E3 ubiquitin ligase activity in animals (Seroogy et al., 2004; Borchers et al., 2002), for this reason, we think that plant PpRMRs could have this function as well, which could contribute to vacuolar targeting. Indeed, I could confirm that PpRMR2 has an E3 ubiquitin ligase activity. PpRMRs substrates are still unknown in moss thus we have analysed putative candidates supposing that they could be ubiquitylated by PpRMRs. We have tested this hypothesis through in vitro ubiquitylation assays, obtaining ambiguous results. In the fourth chapter, I show preliminary results about the visible phenotype of PpRMR-KO mutants: PpWT and PpRMR-KO lines displayed phenotypic differences in leafy gametophores, which were accentuated upon salt stress exposure. Lastly, I transformed the transgenic lines PpWT/Ci-Card and Pp5KO/Ci-Card with mutated versions of PpRMR2 and analysed their effect on vacuolar transport by confocal microscopy. For most of the constructions tested, the trafficking was perturbed in both lines. Only PpWT/Ci-Card expressing PpRMR2ΔSer (lacking the Serine-Rich motif) displayed a typical vacuolar pattern.

scholarly journals E3 ubiquitin ligase MARCHF5 controls BAK apoptotic activity independently of BH3-only proteins

2022 ◽  
Author(s):  
Grant Dewson ◽  
Alan Shuai Huang ◽  
Hui San Chin ◽  
Boris Reljic ◽  
Tirta M Djajawi ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Apoptotic Cell ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligase Activity ◽  
A Genome ◽  
Library Screen ◽  
Important Regulator ◽  
Apoptotic Activity ◽  
Bh3 Mimetic ◽  
Survival Proteins

Intrinsic apoptosis is principally governed by the BCL-2 family of proteins, but some non-BCL-2 proteins are also critical to control this process. To identify novel apoptosis regulators, we performed a genome-wide CRISPR-Cas9 library screen, and identified the mitochondrial E3 ubiquitin ligase MARCHF5/MITOL/RNF153 as an important regulator of BAK apoptotic function. Deleting MARCHF5 in diverse cell lines dependent on BAK conferred profound resistance to BH3-mimetic drugs. The loss of MARCHF5 or its E3 ubiquitin ligase activity surprisingly drove BAK to adopt an activated conformation, with resistance to BH3-mimetics afforded by the formation of inhibitory complexes with pro-survival proteins MCL-1 and BCL-XL. Importantly, these changes to BAK conformation and pro-survival association occurred independently of BH3-only proteins and influence on pro-survival proteins. This study identifies a new mechanism by which MARCHF5 regulates apoptotic cell death and provides new insight into how cancer cells respond to BH3-mimetic drugs. These data also highlight the emerging role of ubiquitin signalling in apoptosis that may be exploited therapeutically.

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 Parkin Phosphorylation and Modulation of Its E3 Ubiquitin Ligase Activity

2004 ◽  
Vol 280 (5) ◽  
pp. 3390-3399 ◽  
Author(s):  
Ayako Yamamoto ◽  
Arno Friedlein ◽  
Yuzuru Imai ◽  
Ryosuke Takahashi ◽  
Philipp J. Kahle ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligase Activity

The serine protease HtrA2/Omi cleaves Parkin and irreversibly inactivates its E3 ubiquitin ligase activity

2009 ◽  
Vol 387 (3) ◽  
pp. 537-542 ◽  
Author(s):  
Hye-Min Park ◽  
Goo-Young Kim ◽  
Min-Kyung Nam ◽  
Geun-Hye Seong ◽  
Chul Han ◽  
...  
Keyword(s):  
Serine Protease ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligase Activity
Sign in / Sign up

Export Citation Format

Share Document