2019
HMGB2 is a negative regulator of telomerase activity in human embryonic stem and progenitor cells
KUČÍREK, Martin, Alireza Jian BAGHERPOOR, Josef JAROŠ, Aleš HAMPL, Michal ŠTROS et. al.Základní údaje
Originální název
HMGB2 is a negative regulator of telomerase activity in human embryonic stem and progenitor cells
Autoři
KUČÍREK, Martin (203 Česká republika), Alireza Jian BAGHERPOOR (203 Česká republika), Josef JAROŠ (203 Česká republika, domácí), Aleš HAMPL (203 Česká republika, domácí) a Michal ŠTROS (203 Česká republika, garant)
Vydání
FASEB Journal, Federation of American Societies for Experimental Biology, 2019, 0892-6638
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10608 Biochemistry and molecular biology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 4.966
Kód RIV
RIV/00216224:14110/19:00108537
Organizační jednotka
Lékařská fakulta
UT WoS
000507466100097
Klíčová slova anglicky
HMGB1; hESCs; neuroectodermal cells; telomeres
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 11. 5. 2020 10:16, Mgr. Tereza Miškechová
Anotace
V originále
High-mobility group box (HMGB)1 and HMGB2 proteins are the subject of intensive research because of their involvement in DNA replication, repair, transcription, differentiation, proliferation, cell signaling, inflammation, and tumor migration. Using inducible, stably transfected human embryonic stem cells (hESCs) capable of the short hairpin RNA-mediated knockdown (KD) of HMGB1 and HMGB2, we provide evidence that deregulation of HMGB1 or HMGB2 expression in hESCs and their differentiated derivatives (neuroectodermal cells) results in distinct modulation of telomere homeostasis. Whereas HMGB1 enhances telomerase activity, HMGB2 acts as a negative regulator of telomerase activity in the cell. Stimulation of telomerase activity in the HMGB2-deficient cells may be related to activation of the PI3K/protein kinase B/ glycogen synthase kinase-313/ I3-catenin signaling pathways by HMGB1, augmented TERT/telomerase RNA subunit transcription, and possibly also because of changes in telomeric repeat-containing RNA (TERRA) and TERRA-polyA(+) transcription. The impact of HMGB1/2 KD on telomerase transcriptional regulation observed in neuroectodermal cells is partially masked in hESCs by their pluripotent state. Our findings on differential roles of HMGB1 and HMGB2 proteins in regulation of telomerase activity may suggest another possible outcome of HMGB1 targeting in cells, which is currently a promising approach aiming at increasing the anticancer activity of cytotoxic agents.
Návaznosti
MUNI/A/1565/2018, interní kód MU |
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NV16-31501A, projekt VaV |
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