The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35

Zanchetta, Melania Eva; Napolitano, L.M.; Maddalo, Danilo; Meroni, Germana

doi:10.1016/j.bbamcr.2017.07.014

Cited by 10 publications

(12 citation statements)

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“…Overexpressing MIG12’s cytoplasmic binding partner, MID1, abolished a TDP-43-driven increase in nuclear MIG12 protein levels in motor neuron-like cells. Since MID1 is an E3 ubiquitin ligase (48,50,51), this could imply that newly synthesized MIG12 is rapidly targeted by MID1 for degradation by the ubiquitin-proteasome system. While MID1 has been implicated in RNA regulation of key molecules in Alzheimer’s and Huntington’s disease (reviewed in (47)), it has not previously been implicated in TDP-43-driven neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

TDP-43 enhances translation of specific mRNAs linked to neurodegenerative disease

Neelagandan

Gonnella

Dang

et al. 2018

Nucleic Acids Research

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The RNA-binding protein TDP-43 is heavily implicated in neurodegenerative disease. Numerous patient mutations in TARDBP, the gene encoding TDP-43, combined with data from animal and cell-based models, imply that altered RNA regulation by TDP-43 causes Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. However, underlying mechanisms remain unresolved. Increased cytoplasmic TDP-43 levels in diseased neurons suggest a possible role in this cellular compartment. Here, we examined the impact on translation of overexpressing human TDP-43 and the TDP-43A315T patient mutant protein in motor neuron-like cells and primary cultures of cortical neurons. In motor-neuron like cells, TDP-43 associates with ribosomes without significantly affecting global translation. However, ribosome profiling and additional assays revealed enhanced translation and direct binding of Camta1, Mig12, and Dennd4a mRNAs. Overexpressing either wild-type TDP-43 or TDP-43A315T stimulated translation of Camta1 and Mig12 mRNAs via their 5′UTRs and increased CAMTA1 and MIG12 protein levels. In contrast, translational enhancement of Dennd4a mRNA required a specific 3′UTR region and was specifically observed with the TDP-43A315T patient mutant allele. Our data reveal that TDP-43 can function as an mRNA-specific translational enhancer. Moreover, since CAMTA1 and DENND4A are linked to neurodegeneration, they suggest that this function could contribute to disease.

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Section: Discussionmentioning

confidence: 99%

TDP-43 enhances translation of specific mRNAs linked to neurodegenerative disease

Neelagandan

Gonnella

Dang

et al. 2018

Nucleic Acids Research

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“…The TRIM protein family is a family of E3 ubiquitin ligases, including TRIM31 [27], TRIM52 [28], TRIM50 [29], and TRIM18 [30], and were found to be related to a broad range of biological and pathological processes via ubiquitination. TRIM55 was also identified as the first ubiquitin ligase to inhibit PPAR expression via posttranslational ubiquitination and to protect against diabetic cardiomyopathy [31].…”

Section: Discussionmentioning

confidence: 99%

miR-378a-3p inhibits ischemia/reperfusion-induced apoptosis in H9C2 cardiomyocytes by targeting TRIM55 via the DUSP1-JNK1/2 signaling pathway

Tan

Shen

Hui-geng

et al. 2020

Aging

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MicroRNAs (miRNAs) are involved in many pathological and biological processes, such as ischemia/reperfusion (I/R) injury by modulating gene expression. Increasing evidence indicates that miR-378a-3p might provide a potential cardioprotective effect against ischemic heart disease. Cell apoptosis is a crucial mechanism in I/R injury. As such, this study evaluated the protective effects and underlying mechanisms of action of miR-378a-3p on H9C2 cardiomyocyte apoptosis following I/R injury. We found that I/R-induced H9C2 cardiomyocytes exhibited a decrease in miR-378a-3p expression, while treatment with a miR-378a-3p mimic suppressed cell apoptosis, JNK1/2 activation, cleavage of PARP and caspase-3, and Bax/Bcl-2 ratio but increased DUSP1 expression, which subsequently inhibited JNK1/2 phosphorylation. TRIM55 was shown to be a target of miR-378a-3p and its downregulation inhibited the miR-378a-3p inhibitor-induced increase in cell apoptosis and JNK1/2 activation. TRIM55 inhibited DUSP1 protein expression through ubiquitination of DUSP1. Moreover, DUSP1 overexpression inhibited the TRIM55 overexpression-induced increase in cell apoptosis and JNK1/2 activation. The protective effect of miR-378a-3p was subsequently confirmed in a rat myocardial I/R model, as evidenced by a decrease in cardiomyocyte apoptosis of cardiomyocytes, TRIM55 expression, and JNK1/2 activation. Taken together, these results suggest that miR-378a-3p may protect against I/R-induced cardiomyocyte apoptosis via TRIM55/DUSP1/JNK signaling.

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“…A recently identified MID1 substrate is the BRCA2-associated factor BRAF35 (also known as HMG20B) (Zanchetta et al, 2017) that was first isolated as part of a large nuclear multi-protein complex containing BRCA2 (Marmorstein et al, 2001).…”

Section: Mid1 and Mid2 Involvement In Cytokinesismentioning

confidence: 99%

“…Strikingly, although BRAF35 protein levels are regulated by the proteasome, atypical linkages are preferred in MID1-mediated ubiquitination, involving K6, K27, and K29 poly-ubiquitin chains. Among them, only K6 poly-ubiquitination promotes BRAF35 proteasomal degradation while K27 and K29 chains have no degradative effects (Zanchetta et al, 2017). The present knowledge does not offer insights to infer the effect of these modifications on BRAF35 (Kulathu and Komander, 2012).…”

Section: Mid1 and Mid2 Involvement In Cytokinesismentioning

confidence: 99%

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Emerging Roles of the TRIM E3 Ubiquitin Ligases MID1 and MID2 in Cytokinesis

Zanchetta

Meroni

2019

Front. Physiol.

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Ubiquitination is a post-translational modification that consists of ubiquitin attachment to target proteins through sequential steps catalysed by activating (E1), conjugating (E2), and ligase (E3) enzymes. Protein ubiquitination is crucial for the regulation of many cellular processes not only by promoting proteasomal degradation of substrates but also re-localisation of cellular factors and modulation of protein activity. Great importance in orchestrating ubiquitination relies on E3 ligases as these proteins recognise the substrate that needs to be modified at the right time and place. Here we focus on two members of the TRIpartite Motif (TRIM) family of RING E3 ligases, MID1, and MID2. We discuss the recent findings on these developmental disease-related proteins analysing the link between their activity on essential factors and the regulation of cytokinesis highlighting the possible consequence of alteration of this process in pathological conditions.

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The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35

Cited by 10 publications

References 50 publications

TDP-43 enhances translation of specific mRNAs linked to neurodegenerative disease

TDP-43 enhances translation of specific mRNAs linked to neurodegenerative disease

miR-378a-3p inhibits ischemia/reperfusion-induced apoptosis in H9C2 cardiomyocytes by targeting TRIM55 via the DUSP1-JNK1/2 signaling pathway

Emerging Roles of the TRIM E3 Ubiquitin Ligases MID1 and MID2 in Cytokinesis

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