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.
Highlights
A breakthrough in understanding transcriptional control mechanisms was furnished by the discovery of co-activators, a diverse array of cellular factors that connect sequence-specific DNA-binding activators to the general transcriptional machinery, or that help activators and the transcriptional apparatus to navigate through the constraints of chromatin
Accumulating evidence suggests that, apart from its co-activator function, ADA3 participates in countless other biological soirees such as chromatin remodelling, cellular proliferation, cellular senescence, DNA damage response (DDR) and, more importantly, it plays a decisive role in embryonic development
Based on these findings, it can be speculated that high-risk viral oncoproteins like HPV16E6 can hijack this multifunctional co-activator to deregulate transcriptional machinery leading to abnormal proliferation of cells [17,19]
Summary
A breakthrough in understanding transcriptional control mechanisms was furnished by the discovery of co-activators, a diverse array of cellular factors that connect sequence-specific DNA-binding activators to the general transcriptional machinery, or that help activators and the transcriptional apparatus to navigate through the constraints of chromatin. Among several co-activators known so far, human ADA3 is an ambidextrous protein. It exhibits tremendous variability in its interacting complexes to regulate a number of cellular processes. New findings have constantly stimulated researchers to put together the puzzle pieces, revealing the biology of hADA3. This review examines the evidence that established ADA3 as a bona fide component of co-activator complex across the species, outlining recent developments in the field to provide unprecedented insight into the ever-expanding functional characteristics of hADA3, and discusses important directions for future research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
