Tale of a multifaceted co-activator, hADA3: from embryogenesis to cancer and beyond

Abstract

Human ADA3, the evolutionarily conserved transcriptional co-activator, remains the unified part of multiple cellular functions, including regulation of nuclear receptor functions, cell proliferation, apoptosis, senescence, chromatin remodelling, genomic stability and chromosomal maintenance. The past decade has witnessed exciting findings leading to considerable expansion in research related to the biology and regulation of hADA3. Embryonic lethality in homozygous knockout Ada3 mouse signifies the importance of this gene product during early embryonic development. Moreover, the fact that it is a novel target of Human Papillomavirus E6 oncoprotein, one of the most prevalent causal agents behind cervical cancer, helps highlight some of the crucial aspects of HPV-mediated oncogenesis. These findings imply the central involvement of hADA3 in regulation of various cellular functional losses accountable for the genesis of malignancy and viral infections. Recent reports also provide evidence for post-translational modifications of hADA3 leading to its instability and contributing to the malignant phenotype of cervical cancer cells. Furthermore, its association with poor prognosis of breast cancer suggests intimate association in the pathogenesis of the disease. Here, we present the first review on hADA3 with a comprehensive outlook on the molecular and functional roles of hADA3 to provoke further interest for more elegant and intensive studies exploring assorted aspects of this protein.

Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

“…The variant was present in all seven affected individuals in the three-generation pedigree, but also present as a heterozygous variant in the unaffected grandfather. This gene is a component of the histone acetyl transferase (HAT) coactivator complex and a regulator of p53 and it is important for chromatin modulation and cell cycle progression 47 . TADA3 is universally highly expressed in brain regions (> 70 TPM in the GTEx data) 30 .…”

“…TADA3 is universally highly expressed in brain regions (> 70 TPM in the GTEx data) 30 . As a multifaceted protein, TADA3 plays an important role in chromatin remodeling, cellular proliferation, cellular senescence, DNA damage response, and embryonic development 47 .…”

Transcriptional adaptor 3 influences the proliferative and invasive phenotypes of non-small cell lung cancer cells via regulating EMT

“…ADA3 has been shown to interact with other various proteins associated with tumorigenesis, including HPV16 E6 protein [27,28] and p53 [29,30]. Additionally, a number of previous studies have identified alterations in ADA3 as contributing factors in diverse cancer types [31]. However, to the best of the authors' knowledge, relatively few studies have investigated the potential contribution of TADA3 to NSCLC.…”

Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases

“… 370 Mirza et al 371 have reported that ADA3 is over expressed in breast cancer patients and as a transcriptional co-activator, human ADA3 (hADA3) interacts with ERα, thereby transactivating its downstream targets leading to breast cancer progression. 372 …”