2012
MicroRNAs regulate P21WAF1 / CIP 1 protein expression and the DNA damage response in human embryonic stem cells (hESCs)
DOLEŽALOVÁ, Dáša; Marek MRÁZ; Vladimír VINARSKÝ; Zuzana HOLUBCOVÁ; Josef JAROŠ et. al.Základní údaje
Originální název
MicroRNAs regulate P21WAF1 / CIP 1 protein expression and the DNA damage response in human embryonic stem cells (hESCs)
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Vydání
ISSCR 10th Annual Meeting, 13.-.16.6.2012, Yokohama, Japonsko, 2012
Další údaje
Jazyk
angličtina
Typ výsledku
Konferenční abstrakt
Stát vydavatele
Japonsko
Utajení
není předmětem státního či obchodního tajemství
Organizační jednotka
Lékařská fakulta
Příznaky
Mezinárodní význam
Změněno: 13. 8. 2012 11:38, Mgr. Martina Vráblíková
Anotace
V originále
Studies of human embryonic stem cells (hESCs) commonly describe the nonfunctional p53-p21 axis of the G1/S checkpoint pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). Importantly, p21 mRNA is clearly present and upregulated after the DDR in hESCs, but p21 protein is not detectable. In this article, we provide evidence that expression of p21 protein is directly regulated by the microRNA (miRNA) pathway under standard culture conditions and after DNA damage. The DDR in hESCs leads to upregulation of tens of miRNAs, including hESC-specific miRNAs such as those of the miR-302 family, miR-371-372 family, or C19MC miRNA cluster. Most importantly, we show that the hESC-enriched miRNA family miR-302 (miR-302a, miR-302b, miR-302c, and miR-302d) directly contributes to regulation of p21 expression in hESCs and, thus, demonstrate a novel function for miR-302s in hESCS. The described mechanism elucidates the role of miRNAs in regulation of important molecular pathway governing the G1/S transition checkpoint before as well as after DNA damage.