scholarly journals E3 Ubiquitin Ligase TRIP12: Regulation, Structure, and Physiopathological Functions

2020 ◽  
Vol 21 (22) ◽  
pp. 8515
Author(s):  
Manon Brunet ◽  
Claire Vargas ◽  
Dorian Larrieu ◽  
Jérôme Torrisani ◽  
Marlène Dufresne
Keyword(s):  
Thyroid Hormone ◽  
Ubiquitin Ligase ◽  
Hormone Receptor ◽  
Cell Cycle Progression ◽  
Thyroid Hormone Receptor ◽  
E3 Ubiquitin Ligase ◽  
Autism Spectrum ◽  
Causative Gene ◽  
Interacting Protein ◽  
C Terminus

The Thyroid hormone Receptor Interacting Protein 12 (TRIP12) protein belongs to the 28-member Homologous to the E6-AP C-Terminus (HECT) E3 ubiquitin ligase family. First described as an interactor of the thyroid hormone receptor, TRIP12’s biological importance was revealed by the embryonic lethality of a murine model bearing an inactivating mutation in the TRIP12 gene. Further studies showed the participation of TRIP12 in the regulation of major biological processes such as cell cycle progression, DNA damage repair, chromatin remodeling, and cell differentiation by an ubiquitination-mediated degradation of key protein substrates. Moreover, alterations of TRIP12 expression have been reported in cancers that can serve as predictive markers of therapeutic response. The TRIP12 gene is also referenced as a causative gene associated to intellectual disorders such as Clark–Baraitser syndrome and is clearly implicated in Autism Spectrum Disorder. The aim of the review is to provide an exhaustive and integrated overview of the different aspects of TRIP12 ranging from its regulation, molecular functions and physio-pathological implications.

Evidence for evolutionary conservation of a physical linkage between the human BAF60b, a subunit of SWI/SNF complex, and thyroid hormone receptor interacting protein-1 genes on chromosome 17

Genome ◽  
1999 ◽  
Vol 42 (3) ◽  
pp. 545-549
Author(s):  
Rama Mohan Surabhi ◽  
Lisa Dawn Daly ◽  
Peter A Cattini
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Evolutionary Conservation ◽  
Chromosome 17 ◽  
N Gene ◽  
Interacting Protein ◽  
Physical Linkage ◽  
A Subunit ◽  
Polyadenylation Sites

The ubiquitously expressed rat BAF60b gene, which codes for a subunit of the multiprotein SWI/SNF complex, was recently identified between the pituitary growth hormone (GH-N) and thyroid hormone receptor interacting protein-1 (TRIP-1) genes. In primates, duplication of the GH-N gene has resulted in the addition of four placenta-specific (GH-V, CS-A, CS-B, and CS-L) genes downstream of the GH-N gene. As part of our study of the effect of remote sequences on the transcriptional regulation of the GH/CS gene family, we showed recently that these genes lie 40 kb upstream of the human TRIP-1 gene. We have now investigated the presence of the human BAF60b gene upstream of the TRIP-1 gene for evidence of evolutionary conservation of this arrangement or its disruption by the recent duplication of the nearby GH-N gene in primates. We report that, as in the rat genome, the human BAF60b gene is in the reverse transcriptional direction relative to the TRIP-1 gene, such that their polyadenylation sites are separated by 93 bp which compares with 92 bp in the rat. Reexamination of reported porcine TRIP-1 sequences also revealed the presence of the BAF60b gene separated by 93 bp, supporting an evolutionary conservation of this arrangement.Key words: P1 clone, gene mapping, downstream gene.

scholarly journals Differential recognition of liganded and unliganded thyroid hormone receptor by retinoid X receptor regulates transcriptional repression.

1997 ◽  
Vol 17 (12) ◽  
pp. 6887-6897 ◽  
Author(s):  
J Zhang ◽  
I Zamir ◽  
M A Lazar
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Transcriptional Repression ◽  
Thyroid Hormone Receptor ◽  
Retinoid X Receptor ◽  
Multiprotein Complexes ◽  
C Terminus ◽  
Differential Recognition ◽  
Dimerization Interface ◽  
Transcriptional Coregulators

Thyroid hormone receptor (TR) functions as part of multiprotein complexes that also include retinoid X receptor (RXR) and transcriptional coregulators. We have found that both the TR CoR box and ninth heptad are required for RXR interaction and in turn for interaction with corepressor proteins N-CoR and SMRT. Remarkably, the recruitment of RXR to repression-defective CoR box and ninth-heptad mutants via a heterologous dimerization interface restores both corepressor interaction and repression. The addition of thyroid hormone obviates the CoR box requirement for RXR interaction, provided that the AF2 activation helix at the C terminus of TR is intact. These results indicate that RXR differentially recognizes the unliganded and liganded conformations of TR and that these differences appear to play a major role in the recruitment of corepressors to TR-RXR heterodimers.

scholarly journals Thyroid Hormone Receptor Interacting Protein 3 (Trip3) Is a Novel Coactivator of Hepatocyte Nuclear Factor-4 

Diabetes ◽  
2002 ◽  
Vol 51 (4) ◽  
pp. 910-914 ◽  
Author(s):  
H. Iwahashi ◽  
K. Yamagata ◽  
I. Yoshiuchi ◽  
J. Terasaki ◽  
Q. Yang ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Interacting Protein ◽  
Hepatocyte Nuclear Factor 4

scholarly journals The tau 4 activation domain of the thyroid hormone receptor is required for release of a putative corepressor(s) necessary for transcriptional silencing.

1995 ◽  
Vol 15 (1) ◽  
pp. 76-86 ◽  
Author(s):  
A Baniahmad ◽  
X Leng ◽  
T P Burris ◽  
S Y Tsai ◽  
M J Tsai ◽  
...  
Keyword(s):  
Amino Acids ◽  
Thyroid Hormone ◽  
Ligand Binding ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Activation Domain ◽  
C Terminus

The C terminus of nuclear hormone receptors is a complex structure that contains multiple functions. We are interested in the mechanism by which thyroid hormone converts its receptor from a transcriptional silencer to an activator of transcription. Both regulatory functions are localized in the ligand binding domain of this receptor superfamily member. In this study, we have identified and characterized several functional domains within the ligand binding domain of the human thyroid hormone receptor (TR beta) conferring transactivation. Interestingly, these domains are localized adjacent to hormone binding sites. One activation domain, designated tau 4, is only 17 amino acids in length and is localized at the extreme C terminus of TR. Deletion of six amino acids of tau 4 resulted in a receptor that could still bind hormone but acted as a constitutive silencer, indicating that tau 4 is required for both transactivation and relief of the silencing functions. In addition, we performed in vivo competition experiments, the results of which suggest that in the absence of tau 4 or hormone, TR is bound by a corepressor protein(s) and that one role of hormone is to release corepressor from the receptor. We propose a general model in which the role of hormone is to induce a conformational change in the receptor that subsequently affects the action of tau 4, leading to both relief of silencing and transcriptional activation.

scholarly journals JMJD2A Is a Novel N-CoR-Interacting Protein and Is Involved in Repression of the Human Transcription Factor Achaete Scute-Like Homologue 2 (ASCL2/Hash2)

2005 ◽  
Vol 25 (15) ◽  
pp. 6404-6414 ◽  
Author(s):  
Dianzheng Zhang ◽  
Ho-Guen Yoon ◽  
Jiemin Wong
Keyword(s):  
Transcription Factor ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Placental Development ◽  
Interaction Domain ◽  
Interacting Protein ◽  
Mouse Tissues

ABSTRACT Corepressor N-CoR (nuclear receptor corepressor) and the highly related protein SMRT (silencing mediator of retinoid and thyroid hormone receptor) play important roles in different biological processes including proliferation, differentiation, and development. Understanding the biological function of these corepressors requires identification and characterization of their interacting proteins. Here we report the characterization of a novel N-CoR-interacting protein, JMJD2A (previously known as KIAA0677). JMJD2A is an evolutionarily conserved nuclear protein containing many functionally unknown domains. JMJD2A directly interacts with the N-terminal region of N-CoR through a small NID (N-CoR interaction domain) both in vitro and in vivo. Despite its copurification with N-CoR, JMJD2A is not a core subunit of the stable multiprotein N-CoR complex and is not required for N-CoR-mediated repression by thyroid hormone receptor. By chromatin immunoprecipitation cloning, we identified the human achaete scute-like homologue 2 (ASCL2/Hash2) gene as a gene regulated by JMJD2A. ASCL2 is a basic helix-loop-helix transcription factor whose mouse homolog is encoded by an imprinted gene highly expressed during the development of extraembroynic trophoblast lineages but repressed in other tissues and is essential for proper placental development. We demonstrated that JMJD2A selectively represses the expression of the ASCL2 gene but not other imprinted genes in the same imprinted locus in HeLa cells and that this repression required a functional N-CoR complex and the tandem Tudor domain of JMJD2A. Like N-CoR, JMJD2A is widely expressed in various mouse tissues. Our data indicate that JMJD2A makes use of the N-CoR complex to repress transcription and suggest that JMJD2A together with N-CoR could play a role in repressing ASCL2 expression in various tissues.

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