Abstract
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.
Highlights
Thyroid hormone Receptor Interacting Protein 12 cDNA was cloned from the human myeloid KG-1 cell line and named the unidentified KIAA0045 human gene
We previously showed that Thyroid hormone Receptor Interacting Protein 12 (TRIP12) interacts with chromatin through an Intrinsically disordered regions (IDR), which corresponds to the N-terminal quarter of the protein (Figure 1), and that the deletion of this domain leads to a loss of TRIP12 interaction with chromatin [7]
We provide a synthesis of the different knowledge on the E3 ubiquitin ligase TRIP12
Summary
Thyroid hormone Receptor Interacting Protein 12 cDNA was cloned from the human myeloid KG-1 cell line and named the unidentified KIAA0045 human gene. Another study identified Thyroid hormone Receptor Interacting Protein 12 (TRIP12) as a member of the structurally and functionally related E3 ubiquitin ligases based on the identification of a domain homologous to the E6-associated protein carboxyl terminus (HECT domain), which is a protein that induces the ubiquitin-dependent degradation of P53 in the presence of the E6 protein from the papillomavirus [2]. Several molecular functions of TRIP12 in important cellular processes and signaling pathways have been demonstrated in recent years. Accumulating evidence indicate that TRIP12 ubiquitinates key proteins for cell homeostasis, regulates gene expression (See Section 5), and plays important roles in cancers and neurological diseases. We attempt to comprehensively summarize the current knowledge from the literature and databases on TRIP12 This summary includes the gene and protein expression, the protein structure, the protein interactors and functions. We discuss the potential role of TRIP12 as a therapeutic target and highlight the need for further research studies on this protein
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