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Pleiotropic roles of tankyrase/PARP proteins in the establishment and maintenance of human naïve pluripotency. | LitMetric

Pleiotropic roles of tankyrase/PARP proteins in the establishment and maintenance of human naïve pluripotency.

Exp Cell Res

Institute for Cell Engineering, And Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 733 N. Broadway, Miller Research Building, Room 755, Baltimore, MD, 21205, United States. Electronic address:

Published: May 2020

AI Article Synopsis

Article Abstract

Tankyrase 1 (TNKS1; PARP-5a) and Tankyrase 2 (TNKS2; PARP-5b) are poly-ADP-ribosyl-polymerase (PARP)-domain-containing proteins that regulate the activities of a wide repertoire of target proteins via post-translational addition of poly-ADP-ribose polymers (PARylation). Although tankyrases were first identified as regulators of human telomere elongation, important and expansive roles of tankyrase activity have recently emerged in the development and maintenance of stem cell states. Herein, we summarize the current state of knowledge of the various tankyrase-mediated activities that may promote human naïve and 'extended' pluripotency'. We review the putative role of tankyrase and PARP inhibition in trophectoderm specification, telomere elongation, DNA repair and chromosomal segregation, metabolism, and PTEN-mediated apoptosis. Importantly, tankyrases possess PARP-independent activities that include regulation of MDC1-associated DNA repair by homologous recombination (HR) and autophagy/pexophagy, which is an essential mechanism of protein synthesis in the preimplantation embryo. Additionally, tankyrases auto-regulate themselves via auto-PARylation which augments their cellular protein levels and potentiates their non-PARP tankyrase functions. We propose that these non-PARP-related activities of tankyrase proteins may further independently affect both naïve and extended pluripotency via mechanisms that remain undetermined. We broadly outline a hypothetical framework for how inclusion of a tankyrase/PARP inhibitor in small molecule cocktails may stabilize and potentiate naïve and extended pluripotency via pleiotropic routes and mechanisms.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171895PMC
http://dx.doi.org/10.1016/j.yexcr.2020.111935DOI Listing

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