HMGB2 is a negative regulator of telomerase activity in human embryonic stem and progenitor cells

18Citations
Citations of this article
15Readers
Mendeley users who have this article in their library.

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-3β/ β-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.—Kučírek, M., Bagherpoor, A. J., Jaroš, J., Hampl, A., Štros, M. HMGB2 is a negative regulator of telomerase activity in human embryonic stem and progenitor cells. FASEB J. 33, 14307-14324 (2019). www.fasebj.org.

References Powered by Scopus

AKT/PKB Signaling: Navigating the Network

2640Citations
N/AReaders
Get full text

PI3K pathway alterations in cancer: Variations on a theme

1609Citations
N/AReaders
Get full text

Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases

1290Citations
N/AReaders
Get full text

Cited by Powered by Scopus

The role of high mobility group protein B3 (HMGB3) in tumor proliferation and drug resistance

36Citations
N/AReaders
Get full text

The Redox Protein High-Mobility Group Box 1 in Cell Death and Cancer

9Citations
N/AReaders
Get full text

High-mobility group box 2 reflects exacerbated disease characteristics and poor prognosis in non-small cell lung cancer patients

7Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Kučírek, M., Bagherpoor, A. J., Jaroš, J., Hampl, A., & Štros, M. (2019). HMGB2 is a negative regulator of telomerase activity in human embryonic stem and progenitor cells. FASEB Journal, 33(12), 14307–14324. https://doi.org/10.1096/fj.201901465RRR

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 7

78%

Lecturer / Post doc 1

11%

Researcher 1

11%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 5

45%

Medicine and Dentistry 4

36%

Pharmacology, Toxicology and Pharmaceut... 1

9%

Computer Science 1

9%

Save time finding and organizing research with Mendeley

Sign up for free