KUČÍREK, Martin, Alireza Jian BAGHERPOOR, Josef JAROŠ, Aleš HAMPL and Michal ŠTROS. HMGB2 is a negative regulator of telomerase activity in human embryonic stem and progenitor cells. FASEB Journal. Federation of American Societies for Experimental Biology, 2019, vol. 33, No 12, p. 14307-14324. ISSN 0892-6638. Available from: https://dx.doi.org/10.1096/fj.201901465RRR.
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Basic information
Original name HMGB2 is a negative regulator of telomerase activity in human embryonic stem and progenitor cells
Authors KUČÍREK, Martin (203 Czech Republic), Alireza Jian BAGHERPOOR (203 Czech Republic), Josef JAROŠ (203 Czech Republic, belonging to the institution), Aleš HAMPL (203 Czech Republic, belonging to the institution) and Michal ŠTROS (203 Czech Republic, guarantor).
Edition FASEB Journal, Federation of American Societies for Experimental Biology, 2019, 0892-6638.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 4.966
RIV identification code RIV/00216224:14110/19:00108537
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1096/fj.201901465RRR
UT WoS 000507466100097
Keywords in English HMGB1; hESCs; neuroectodermal cells; telomeres
Tags 14110517, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 11/5/2020 10:16.
Abstract
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.
Links
MUNI/A/1565/2018, interní kód MUName: Zdroje pro tkáňové inženýrství 9 (Acronym: TissueEng 9)
Investor: Masaryk University, Category A
NV16-31501A, research and development projectName: Tkáňové inženýrství epitelů: Buňky a protokoly pro regenerativní medicínu
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