The MID1 protein is a central player during development and in disease

Winter, Jennifer; Mf, Basilicata; Mp, Stemmler; Krauß, Sybille

doi:10.2741/4413

Cited by 29 publications

(12 citation statements)

References 81 publications

(120 reference statements)

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“…Unlike CAMTA1 and DENND4a, no direct connection between MIG12 and neurodegenerative disease has previously been described. However, several lines of evidence support a role for MIG12’s protein-protein interaction partner, MID1, in both neurodevelopmental disorders and neurodegenerative disease (47). MID1 is a cytoplasmic protein whose molecular functions include E3 ubiquitin ligase activity and regulation of translation through direct and indirect mechanisms (47–51).…”

Section: Resultsmentioning

confidence: 99%

“…However, several lines of evidence support a role for MIG12’s protein-protein interaction partner, MID1, in both neurodevelopmental disorders and neurodegenerative disease (47). MID1 is a cytoplasmic protein whose molecular functions include E3 ubiquitin ligase activity and regulation of translation through direct and indirect mechanisms (47–51). This suggests that MID1 binding to MIG12 could affect MIG12 protein levels, and that this could be a potential connection between altered Mig12 mRNA translation and neurodegenerative disease.…”

Section: Resultsmentioning

confidence: 99%

“…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. Our data suggest it would be interesting to see how MID1 is regulated in ALS/FTD and how this may relate to TDP-43’s effects on Mig12 mRNA translation.…”

Section: Discussionmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Neelagandan

Gonnella

Dang

et al. 2018

Nucleic Acids Research

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“…In more physiological contexts, both unique and common MID proteins partners have been identified, some of which are reported as MID E3 ligases bona fide substrates. These data are briefly summarised in Table 1 and recently thoroughly reviewed in Li et al (2016); Winter et al (2016). These findings suggest that the two TRIM paralogues evolved maintaining common roles while developing their own specificity, likely in a context-specific manner.…”

Section: Introductionmentioning

confidence: 91%

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 RING finger protein MID1 is involved in fundamental cellular processes including somatic cell growth and proliferation as well as neuron function (reviewed in [ 1 ]). Acting as E3 ubiquitin ligase MID1 marks the mTOR antagonist protein phosphatase 2A (PP2A) for degradation by the proteasome and thereby enhances mTOR activity [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs miR-19, miR-340, miR-374 and miR-542 regulate MID1 protein expression

et al. 2018

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The MID1 ubiquitin ligase activates mTOR signaling and regulates mRNA translation. Misregulation of MID1 expression is associated with various diseases including midline malformation syndromes, cancer and neurodegenerative diseases. While this indicates that MID1 expression must be tightly regulated to prevent disease states specific mechanisms involved have not been identified. We examined miRNAs to determine mechanisms that regulate MID1 expression. MicroRNAs (miRNA) are small non-coding RNAs that recognize specific sequences in their target mRNAs. Upon binding, miRNAs typically downregulate expression of these targets. Here, we identified four miRNAs, miR-19, miR-340, miR-374 and miR-542 that bind to the 3’-UTR of the MID1 mRNA. These miRNAs not only regulate MID1 expression but also mTOR signaling and translation of disease associated mRNAs and could therefore serve as potential drugs for future therapy development.

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The MID1 protein is a central player during development and in disease

Cited by 29 publications

References 81 publications

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

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

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

MicroRNAs miR-19, miR-340, miR-374 and miR-542 regulate MID1 protein expression

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