Last update 19 Sep 2024

TBL3

Last update 19 Sep 2024

Basic Info

Synonyms

SAZD, TBL3, transducin beta like 3

+ [3]

Introduction

Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Drugs associated with TBL3

IMT-400

Target

TBL3

Mechanism

TBL3 modulators

Active Org.

TrueBinding, Inc.Startup

Originator Org.

TrueBinding, Inc.Startup

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TBL3

100 Translational Medicine associated with TBL3

0 Patents (Medical) associated with TBL3

Literatures (Medical) associated with TBL3

01 Aug 2024·Genes, Chromosomes and Cancer

TLE3 Is a Novel Fusion Partner of JAK2 in Myeloid/Lymphoid Neoplasm With Eosinophilia Responding to JAK2 Inhibition

Article

Author: Lazarevic, Vladimir ; Orsmark‐Pietras, Christina ; Olsson‐Arvidsson, Linda ; Lilljebjörn, Henrik ; Ågerstam, Helena

ABSTRACTChromosomal rearrangements involving Janus kinase 2 (JAK2) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of JAK2 fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co‐repressor‐encoding gene transducin‐like enhancer of split 3 (TLE3) and JAK2 in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in PTPN11 and NRAS. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T‐cell leukemia/lymphoma. The present case shows similarities to previously reported cases with PCM1::JAK2 and BCR::JAK2 with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other JAK2 fusion genes may benefit from treatment with JAK2 inhibitors.

01 Aug 2023·Molecular and Cellular Endocrinology

HHEX suppresses advanced thyroid cancer by interacting with TLE3

Article

Author: Wang, Hui ; Fu, Hongliang ; Jin, Hongfu ; Han, Yali ; Feng, Fang ; Xu, Zhongyun ; Feng, Yiyuan ; Huang, Shuo ; Chen, Yuanyuan ; Yan, Yeqing ; Yin, Yafu ; Huang, Yueye ; Cheng, Weiwei

Haematopoietically Expressed Homeobox (HHEX) gene is highly expressed in the thyroid gland and plays critical roles in the development and differentiation of the thyroid gland. While it has been indicated to be downregulated in thyroid cancer, its function and the underlying mechanism remain unclear. Herein, we observed low expression and aberrant cytoplasmic localization of HHEX in thyroid cancer cell lines. Knockdown of HHEX significantly enhanced cell proliferation, migration and invasion, while overexpression of HHEX showed the opposite effects in vitro and in vivo. These data provide evidence that HHEX is a tumor suppressor in thyroid cancer. Additionally, our results showed that HHEX overexpression upregulated the expression of sodium iodine symporter (NIS) mRNA and also enhanced NIS promoter activity, suggesting a favorable effect of HHEX in promoting thyroid cancer differentiation. Mechanistically, HHEX exerted a regulatory effect on the expression of transducin-like enhancer of split 3 (TLE3) protein, which inhibited the Wnt/β-catenin signaling pathway. Nuclear localized HHEX bound to and upregulated TLE3 expression by preventing TLE3 protein from being distributed to the cytoplasm and being ubiquitinated. In conclusion, our study suggested that restoring HHEX expression has the potential to be a new strategy in the treatment of advanced thyroid cancer.

01 Aug 2023·The FASEB Journal

Zeb1 and Tle3 are trans‐factors that differentially regulate the expression of myosin heavy chain‐embryonic and skeletal muscle differentiation

Article

Author: Zehra, Aatifa ; Mathew, Sam J ; Saini, Masum ; Kumar, Pankaj

AbstractMyosin heavy chain‐embryonic encoded by the Myh3 gene is a skeletal muscle‐specific contractile protein expressed during mammalian development and regeneration, essential for proper myogenic differentiation and function. It is likely that multiple trans‐factors are involved in this precise temporal regulation of Myh3 expression. We identify a 4230 bp promoter‐enhancer region that drives Myh3 transcription in vitro during C2C12 myogenic differentiation and in vivo during muscle regeneration, including sequences both upstream and downstream of the Myh3 TATA‐box that are necessary for complete Myh3 promoter activity. Using C2C12 mouse myogenic cells, we find that Zinc‐finger E‐box binding homeobox 1 (Zeb1) and Transducin‐like Enhancer of Split 3 (Tle3) proteins are crucial trans‐factors that interact and differentially regulate Myh3 expression. Loss of Zeb1 function results in earlier expression of myogenic differentiation genes and accelerated differentiation, whereas Tle3 depletion leads to reduced expression of myogenic differentiation genes and impaired differentiation. Tle3 knockdown resulted in downregulation of Zeb1, which could be mediated by increased expression of miR‐200c, a microRNA that binds to Zeb1 transcript and degrades it. Tle3 functions upstream of Zeb1 in regulating myogenic differentiation since double knockdown of Zeb1 and Tle3 resulted in effects seen upon Tle3 depletion. We identify a novel E‐box in the Myh3 distal promoter‐enhancer region, where Zeb1 binds to repress Myh3 expression. In addition to regulation of myogenic differentiation at the transcriptional level, we uncover post‐transcriptional regulation by Tle3 to regulate MyoG expression, mediated by the mRNA stabilizing Human antigen R (HuR) protein. Thus, Tle3 and Zeb1 are essential trans‐factors that differentially regulate Myh3 expression and C2C12 cell myogenic differentiation in vitro.

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TBL3

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