Protein Phosphatase 2A (PP2A)-specific Ubiquitin Ligase MID1 Is a Sequence-dependent Regulator of Translation Efficiency Controlling 3-Phosphoinositide-dependent Protein Kinase-1 (PDPK-1)

Aranda-Orgillés, Beatriz; Rutschow, Désirée; Zeller, Raphael; Karagiannidis, Antonios I.; Köhler, Andrea; Chen, Changwei; Wilson, Timothy J.; Krause, Sven; Roepcke, Stefan; Lilley, David M. J.; Schneider, Rainer; Schweiger, Susann

doi:10.1074/jbc.m111.224451

Cited by 28 publications

(54 citation statements)

References 53 publications

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“…As we have shown previously MID1 and a4 stimulate translation of mRNAs that are associated with the MID1 protein complex 16 . Here we demonstrate that the MID1 protein together with its interaction partners PP2A and S6K binds mutant HTT mRNA via its elongated CAG repeats.…”

supporting

confidence: 64%

“…S1). The MID1 protein complex binds mRNAs through G-rich RNA motifs forming stable secondary structures 16,17,26 . Thus, CAG repeat stretches, which are G-rich structures and form stable hairpins, could be recognized by the MID1-complex.…”

Section: Mid1mentioning

confidence: 99%

“…The experiments described above, and the role of the MID1 protein complex in the regulation of translation efficiency of mRNAs specifically attached to it 16 made us hypothesize that (i) the MID1-complex could control the translation of mRNAs with expanded CAG repeats, and (ii) the amount of protein that is synthesized from a CAG repeat containing mRNA increases with the length of the repeat.…”

Section: Mid1mentioning

confidence: 99%

“…One of such mRNP complexes contains the MID1 protein, the catalytic subunit of protein phosphatase 2A (PP2Ac) and 40S ribosomal S6 kinase (S6K), a target of mammalian target of rapamycin (mTOR) kinase and PP2A 16,17 . MID1 is a ubiquitin ligase that binds the a4 protein, a regulatory subunit of PP2A.…”

mentioning

confidence: 99%

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Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex

et al. 2013

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Expansion of CAG repeats is a common feature of various neurodegenerative disorders, including Huntington's disease. Here we show that expanded CAG repeats bind to a translation regulatory protein complex containing MID1, protein phosphatase 2A and 40S ribosomal S6 kinase. Binding of the MID1-protein phosphatase 2A protein complex increases with CAG repeat size and stimulates translation of the CAG repeat expansion containing messenger RNA in a MID1-, protein phosphatase 2A-and mammalian target of rapamycindependent manner. Our data indicate that pathological CAG repeat expansions upregulate protein translation leading to an overproduction of aberrant protein and suggest that the MID1-complex may serve as a therapeutic target for the treatment of CAG repeat expansion disorders.

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supporting

confidence: 64%

Section: Mid1mentioning

confidence: 99%

Section: Mid1mentioning

confidence: 99%

mentioning

confidence: 99%

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Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex

et al. 2013

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“…In their native tandem configuration, the activity of the RING domain is significantly enhanced by the B-boxes implying cooperativity in function (19). The interaction between ␣4 and MID1 is mediated by the C-terminal domain (residues 236 -280) of ␣4 and the Bbox1 domain of MID1, whereas the N-terminal domain (residues 1-236) of ␣4 is involved in binding PP2Ac (15,20,21).…”

Section: Alpha4 (␣4) Is a Key Regulator Of Protein Phosphatase 2a (Ppmentioning

confidence: 99%

The MID1 E3 Ligase Catalyzes the Polyubiquitination of Alpha4 (α4), a Regulatory Subunit of Protein Phosphatase 2A (PP2A)

Huang²,

Zaghlula

et al. 2013

Journal of Biological Chemistry

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Background: IGBP1/␣4 interacts with microtubule-associated MID1 to regulate PP2A within the mTOR pathway. Results: MID1 catalyzes the polyubiquitination and degradation of ␣4, demonstrating for the first time a mechanism for ␣4 regulation. Conclusion:The tandem RING-Bbox domains are required for ␣4 polyubiquitination and degradation. Significance: Ectopic overexpression of IGBP1/␣4 transforms cells. Ubiquitination of ␣4 impacts the stability and activity level of PP2A.

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Ubiquitin Signaling Regulates RNA Biogenesis, Processing, and Metabolism

2019

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The fate of eukaryotic proteins, from their synthesis to destruction, is supervised by the ubiquitin–proteasome system (UPS). The UPS is the primary pathway responsible for selective proteolysis of intracellular proteins, which is guided by covalent attachment of ubiquitin to target proteins by E1 (activating), E2 (conjugating), and E3 (ligating) enzymes in a process known as ubiquitylation. The UPS can also regulate protein synthesis by influencing multiple steps of RNA (ribonucleic acid) metabolism. Here, recent publications concerning the interplay between the UPS and different types of RNA are reviewed. This interplay mainly involves specific RNA‐binding E3 ligases that link RNA‐dependent processes with protein ubiquitylation. The emerging understanding of their modes of RNA binding, their RNA targets, and their molecular and cellular functions are primarily focused on. It is discussed how the UPS adapted to interact with different types of RNA and how RNA molecules influence the ubiquitin signaling components.

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Protein Phosphatase 2A (PP2A)-specific Ubiquitin Ligase MID1 Is a Sequence-dependent Regulator of Translation Efficiency Controlling 3-Phosphoinositide-dependent Protein Kinase-1 (PDPK-1)

Cited by 28 publications

References 53 publications

Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex

Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex

The MID1 E3 Ligase Catalyzes the Polyubiquitination of Alpha4 (α4), a Regulatory Subunit of Protein Phosphatase 2A (PP2A)

Ubiquitin Signaling Regulates RNA Biogenesis, Processing, and Metabolism

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