scholarly journals Competitive ubiquitination activates the tumor suppressor p53

2019 ◽  
Vol 27 (6) ◽  
pp. 1807-1818 ◽  
Author(s):  
Xingyao Li ◽  
Mengqi Guo ◽  
Lun Cai ◽  
Tingting Du ◽  
Ying Liu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Catalytic Activity ◽  
Tumor Suppressor ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Activating Transcription Factor 3 ◽  
Tumor Suppressor P53 ◽  
Unknown Mechanism ◽  
P53 Activation ◽  
Activating Transcription Factor

AbstractBlocking p53 ubiquitination through disrupting its interaction with MDM2 or inhibiting the MDM2 catalytic activity is the central mechanism by which the tumor suppressor p53 is activated in response to genotoxic challenges. Although MDM2 is first characterized as the major E3 ubiquitin ligase for p53, it can also catalyze the conjugation of ubiquitin moieties to other proteins (e.g., activating transcription factor 3, or ATF3). Here we report that ATF3 can act as an ubiquitin “trap” and competes with p53 for MDM2-mediated ubiquitination. While ATF3-mediated p53 stabilization required ATF3 binding to the MDM2 RING domain, we demonstrated that ATF3 ubiquitination catalyzed by MDM2 was indispensable for p53 activation in response to DNA damage. Moreover, a cancer-derived ATF3 mutant (R88G) devoid of ubiquitination failed to prevent p53 from MDM2-mediated degradation and thus was unable to activate the tumor suppressor. Therefore, we have identified a previously-unknown mechanism that can activate p53 in the genotoxic response.

scholarly journals E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis

2014 ◽  
Vol 21 (11) ◽  
pp. 1792-1804 ◽  
Author(s):  
Ju Liu ◽  
C Zhang ◽  
X L Wang ◽  
P Ly ◽  
V Belyi ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Tumor Suppressor P53

Abstract 1229: E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis

2015 ◽  
Author(s):  
Cen Zhang ◽  
Juan Liu ◽  
Xiaolong Wang ◽  
Ken H. Young ◽  
Wenwei Hu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Tumor Suppressor P53

scholarly journals Activating transcription factor 3 is downregulated in hepatocellular carcinoma and functions as a tumor suppressor by regulating cyclin D1

2016 ◽  
Vol 11 (1) ◽  
pp. 367-371 ◽  
Author(s):  
Zheng-xia Wang ◽  
Si-neng Yin ◽  
Gang Tian ◽  
Xian-lin Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Tumor Suppressor ◽  
Cyclin D1 ◽  
Real Time ◽  
Real Time Pcr ◽  
Activating Transcription Factor 3 ◽  
Activating Transcription Factor ◽  
Transcription Factor 3

AbstractObjectivesTo investigate the expression as well as biological roles of activating transcription factor 3 (ATF3) in human hepatocellular carcinoma (HCC) cells.MethodsReal time PCR and western blot were applied to detect the expression of ATF3 in human HCC specimens. MTT assay was used to analyze cell proliferation after ATF3 was overexpressed. The expression of cyclin D1 was detected by real time PCR in ATF3-silenced/-overexpressed cells and HCC samples. Correlation coefficient was finally analyzed between ATF3 and cyclin D1 in the HCC samples.ResultsThe expression of ATF3 was found to be downregulated in tested HCC specimens. Cellular MTT assays showed that cell proliferation was suppressed in ATF3-overexpressing HepG2 cells. In addition, cyclin D1 gene expression exhibited negative correlation with ATF3 in both cell lines and tissue samples.ConclusionLow expression of ATF3 may function as a tumor suppressor via inhibiting cyclin D1 in HCC.

scholarly journals Hakai is required for stabilization of core components of the m6A mRNA methylation machinery

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Praveen Bawankar ◽  
Tina Lence ◽  
Chiara Paolantoni ◽  
Irmgard U. Haussmann ◽  
Migle Kazlauskiene ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Sex Determination ◽  
Ubiquitin Ligase ◽  
Mammalian Cells ◽  
E3 Ubiquitin Ligase ◽  
Human Cells ◽  
Biological Functions ◽  
Mrna Metabolism ◽  
Mrna Methylation ◽  
Core Components

AbstractN6-methyladenosine (m6A) is the most abundant internal modification on mRNA which influences most steps of mRNA metabolism and is involved in several biological functions. The E3 ubiquitin ligase Hakai was previously found in complex with components of the m6A methylation machinery in plants and mammalian cells but its precise function remained to be investigated. Here we show that Hakai is a conserved component of the methyltransferase complex in Drosophila and human cells. In Drosophila, its depletion results in reduced m6A levels and altered m6A-dependent functions including sex determination. We show that its ubiquitination domain is required for dimerization and interaction with other members of the m6A machinery, while its catalytic activity is dispensable. Finally, we demonstrate that the loss of Hakai destabilizes several subunits of the methyltransferase complex, resulting in impaired m6A deposition. Our work adds functional and molecular insights into the mechanism of the m6A mRNA writer complex.

scholarly journals An E3 Ubiquitin Ligase RNF139 Serves as a Tumor-Suppressor in Glioma

2021 ◽  
Author(s):  
Xiaofeng Chen ◽  
Weiping Kuang ◽  
Yong Zhu ◽  
Bin Zhou ◽  
Xiaosong Li ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Ubiquitin Ligase ◽  
Glioma Cell ◽  
Protein Modification ◽  
E3 Ubiquitin Ligase ◽  
Ring Finger ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Tissue Samples

AbstractGlioma is highly lethal because of its high malignancy. Ubiquitination, a type of ubiquitin-dependent protein modification, has been reported to play an oncogenic or tumor-suppressive role in glioma development, depending on the targets. Ring finger protein 139 (RNF139) is a membrane-bound E3 ubiquitin ligase serving as a tumor suppressor by ubiquitylation-dependently suppressing cell growth. Herein, we firstly confirmed the abnormal downregulation of RNF139 in glioma tissues and cell lines. In glioma cells, ectopic RNF139 overexpression could inhibit, whereas RNF139 knockdown could aggravate the aggressive behaviors of glioma cells, including hyperproliferation, migration, and invasion. Moreover, in two glioma cell lines, RNF139 overexpression inhibited, whereas RNF139 knockdown enhanced the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and AKT serine/threonine kinase 1 (AKT). In a word, we demonstrate the aberration in RNF139 expression in glioma tissue samples and cell lines. RNF139 serves as a tumor-suppressor in glioma by inhibiting glioma cell proliferation, migration, and invasion and promoting glioma cell apoptosis through regulating PI3K/AKT signaling.

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