The E3 Ubiquitin Ligase Thyroid Hormone Receptor-interacting Protein 12 Targets Pancreas Transcription Factor 1a for Proteasomal Degradation

Hanoun, Naı̈ma; Fritsch, Samuel; Gayet, Odile; Gigoux, Véronique; Cordelier, Pierre; Dusetti, Nelson; Torrisani, Jérôme; Dufresne, Marlène

doi:10.1074/jbc.m114.620104

Cited by 21 publications

(26 citation statements)

References 36 publications

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“…Recent studies have revealed a few potential binding partners for TRIP12, including amyloid precursor protein-binding protein (APP-BP1) (Park et al 2008); ADP-ribosylation factor 1 (ARF) (Chen et al 2013; Velimezi et al 2013); pancreas transcription factor 1a (PTF1a) (Hanoun et al 2014); SRY (Sex determining region Y)-Box 6 (SOX6) (An et al 2013); HECT, UBA, and WWE domain containing 1, E3 ubiquitin protein ligase (HUWE1) (Poulsen et al 2012); and ring finger protein 168 (RNF168) (Gudjonsson et al 2012), suggesting that TRIP12 plays an important role in a broad range of physiological processes. TRIP12 has been shown also to regulate DNA repair, cell growth, and ARF-P53 pathway related oncogenic stress (Chen et al 2010; Chen et al 2013; Gudjonsson et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Haploinsufficiency of the E3 ubiquitin-protein ligase gene TRIP12 causes intellectual disability with or without autism spectrum disorders, speech delay, and dysmorphic features

et al. 2017

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Impairment of ubiquitin-proteasome system activity involving ubiquitin ligase genes UBE3A, UBE3B, and HUWE1 and deubiquitinating enzyme genes USP7 and USP9X has been reported in patients with neurodevelopmental delays. To date, only handful of single nucleotide variants (SNVs) and copy-number variants (CNVs) involving TRIP12, encoding a member of the HECT domain E3 ubiquitin ligases family on chromosome 2q36.3 have been reported. Using chromosomal microarray analysis (CMA) and whole exome sequencing (WES), we have identified, respectively, five deletion CNVs and four inactivating SNVs (two frameshifts, one missense, and one splicing) in TRIP12. Seven of these variants were found to be de novo; parental studies could not be completed in two families. Quantitative PCR analyses of the splicing mutation showed a dramatically decreased level of TRIP12 mRNA in the proband compared to the family controls, indicating a loss-of-function (LoF) mechanism. The shared clinical features include intellectual disability with or without autistic spectrum disorders, speech delay, and facial dysmorphism. Our findings demonstrate that E3 ubiquitin ligase TRIP12 plays an important role in nervous system development and function. The nine presented pathogenic variants further document that TRIP12 haploinsufficiency causes childhood-onset neurodevelopmental disorder. Finally, our data enable expansion of the phenotypic spectrum of ubiquitin-proteasome dependent disorders.

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Section: Discussionmentioning

confidence: 99%

Haploinsufficiency of the E3 ubiquitin-protein ligase gene TRIP12 causes intellectual disability with or without autism spectrum disorders, speech delay, and dysmorphic features

et al. 2017

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“…Regarding TR, there is only one report [ 55 ] showing that the TR number and positioning changed in pancreatic β cell of postnatal rats, which will be discussed below. A recent study [ 56 ] showed that thyroid hormone receptor-interacting protein (TRIP) 12, an E3 ubiquitin-protein ligase, is a recently discovered component of pancreas transcription factor 1a (PTF1a), which plays a crucial role in the pancreas early development and in the maintenance of the acinar cell phenotype. TRIP12 can play a role in PTF1a downregulation induced by T3, which suggests that TR β is unfavorable for pancreas endocrine development.…”

Section: Thyroid Hormone and Pancreas Developmentmentioning

confidence: 99%

The Roles of Thyroid and Thyroid Hormone in Pancreas: Physiology and Pathology

Chen

Xie

Shen

et al. 2018

International Journal of Endocrinology

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It is widely accepted that thyroid hormones (THs), secreted from the thyroid, play important roles in energy metabolism. It is also known that THs also alter the functioning of other endocrine glands; however, their effects on pancreatic function have not yet been reviewed. One of the main functions of the pancreas is insulin secretion, which is altered in diabetes. Diabetes, therefore, could be related to thyroid dysfunction. Earlier research on this subject focused on TH regulation of pancreas function (such as insulin secretion) or on insulin function through TH-mediated increase of energy metabolism. Afterwards, epidemiological investigations and animal test research found a link between autoimmune diseases, thyroid dysfunction, and pancreas pathology; however, the underlying mechanisms remain unknown. Furthermore, recent studies have shown that THs also play important roles in pancreas development and on islet pathology, both in diabetes and in pancreatic cancer. Therefore, an overview of the effects of thyroid and THs on pancreas physiology and pathology is presented. The topics contained in this review include a summary of the relationship between autoimmune thyroid dysfunction and autoimmune pancreas lesions and the effects of THs on pancreas development and pancreas pathology (diabetes and pancreatic cancer).

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“…For example, TRIP12 may serve as an oncogenic drug target for patients with acute myeloid leukemia (AML) by blocking a TRIP12 alternative splicing event, specifically excising exon3 from the mature TRIP12 mRNA [98]. TRIP12 also targets pancreas transcription factor 1a (PTF1a) for proteasomal degradation, a protein essential for pancreatic cancer development [99]. TRIP12 forms a ternary complex with deubiquitylase ubiquitin-specific protease 7 (USP7) that aids in hepatocellular carcinoma (HCC) proliferation; when USP7 expression levels are heightened, TRIP12 cannot tag ARF tumor suppressor (p14ARF) for ubiquitylation [100].…”

Section: Trip12 the Multifunctioning E3 Ubiquitin Ligase Essential Fmentioning

confidence: 99%

New Discoveries on the Roles of “Other” HECT E3 Ubiquitin Ligases in Disease Development

Kane¹,

Spratt²

2020

Ubiquitin - Proteasome Pathway

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HECT E3 ubiquitin ligases selectively recognize, bind, and ubiquitylate their substrate proteins to target them for 26S proteasomal degradation. There is increasing evidence that HECT E3 ubiquitin ligase dysfunction due to misfolding and/or the gene encoding the protein being mutated is responsible for the development of different diseases. Apart from the more prominent and well-characterized E6AP and members of the NEDD4 family, new studies have begun to reveal how other members of the HECT E3 ubiquitin ligase family function as well as their links to disease and developmental disorders. This chapter provides a comprehensive discussion on the more mysterious members of the HECT E3 ubiquitin ligase family and how they control intracellular processes. Specifically, AREL1, HACE1, HECTD1, HECTD4, G2E3, and TRIP12 will be examined as these enzymes have recently been identified as contributors to disease development.2 covalently attach ubiquitin on to a lysine residue of the substrate protein forming a stable isopeptide bond between the C-terminus of ubiquitin and the ε-amine of the substrate lysine [3,5,6]. This process can be repeated numerous times to form different polyubiquitin chain linkages with the specific HECT E3 ubiquitin ligase dictating the type(s) of ubiquitin linkages that are built [2,7]. Chain typesLinker Proposed function Monoubiquitylation Monoubiquitylation/ multi-monoubiquitylation Endocytosis [9] DNA damage repair [10-15] Histone regulation [10-15] Mitophagy [10-15] Protein localization [10-15] Protein interactions [10-15] Protein transportation [10-15] Transcription activation [10-15] Polyubiquitylation Chain (homotypic) M1 Innate immunity [2, 9, 16] Linear chain formation [9] NF-κB activation [9, 16] Signaling cascades [9, 16] K6 DNA damage response [14] NF-κB regulation [14] Mitophagy [14] K11 Cell cycle regulation [17] DNA damage response [18] Mitophagy [17] NF-κB activation [16] Protein degradation [17] K27 DNA damage response [18] Kinase activation [19] Protein degradation [20] Protein scaffolding [21] Protein trafficking [22] K29 DNA damage response [18] Kinase activation [19] Protein degradation [9] K33 DNA damage response [10-15, 18] Kinase activation [23] Post-golgi trafficking [24] T-cell signaling [23] K4 8 Protein degradation [1, 2, 25] K63 DNA damage response [9, 18] NF-κB activation [9, 16] Protein trafficking [9] Chain (heterotypic; branched) M1 /K63 NF-κB activation [16] K11 /K4 8 Protein degradation [26, 27] K29/K48 Protein degradation [26] K48/K63 Protein degradation [26] K11 /K63 Endocytosis [28]

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The E3 Ubiquitin Ligase Thyroid Hormone Receptor-interacting Protein 12 Targets Pancreas Transcription Factor 1a for Proteasomal Degradation

Cited by 21 publications

References 36 publications

Haploinsufficiency of the E3 ubiquitin-protein ligase gene TRIP12 causes intellectual disability with or without autism spectrum disorders, speech delay, and dysmorphic features

Haploinsufficiency of the E3 ubiquitin-protein ligase gene TRIP12 causes intellectual disability with or without autism spectrum disorders, speech delay, and dysmorphic features

The Roles of Thyroid and Thyroid Hormone in Pancreas: Physiology and Pathology

New Discoveries on the Roles of “Other” HECT E3 Ubiquitin Ligases in Disease Development

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