PMID- 31661640
OWN - NLM
STAT- MEDLINE
DCOM- 20200608
LR  - 20220623
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 33
IP  - 12
DP  - 2019 Dec 1
TI  - HMGB2 is a negative regulator of telomerase activity in human embryonic stem and 
      progenitor cells.
PG  - 14307-14324
LID - 10.1096/fj.201901465RRR [doi]
AB  - 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-3beta/beta-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.-Kucirek, M., Bagherpoor, A. J., Jaros, J., Hampl, A., Stros, M. HMGB2 is 
      a negative regulator of telomerase activity in human embryonic stem and 
      progenitor cells.
FAU - Kucirek, Martin
AU  - Kucirek M
AD  - Laboratory of Analysis of Chromosomal Proteins, Department of Cell Biology and 
      Radiobiology, Institute of Biophysics of the Czech Academy of Sciences, Brno, 
      Czech Republic.
FAU - Bagherpoor, Alireza J
AU  - Bagherpoor AJ
AD  - Laboratory of Analysis of Chromosomal Proteins, Department of Cell Biology and 
      Radiobiology, Institute of Biophysics of the Czech Academy of Sciences, Brno, 
      Czech Republic.
FAU - Jaros, Josef
AU  - Jaros J
AD  - Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 
      Brno, Czech Republic.
AD  - Cell and Tissue Regeneration, International Clinical Research Center, St. Anne's 
      University Hospital, Brno, Czech Republic.
FAU - Hampl, Ales
AU  - Hampl A
AD  - Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 
      Brno, Czech Republic.
AD  - Cell and Tissue Regeneration, International Clinical Research Center, St. Anne's 
      University Hospital, Brno, Czech Republic.
FAU - Stros, Michal
AU  - Stros M
AD  - Laboratory of Analysis of Chromosomal Proteins, Department of Cell Biology and 
      Radiobiology, Institute of Biophysics of the Czech Academy of Sciences, Brno, 
      Czech Republic.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191026
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, human)
RN  - 0 (HMGB2 Protein)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Cell Differentiation
MH  - HMGB1 Protein/genetics
MH  - HMGB2 Protein/genetics/*physiology
MH  - Human Embryonic Stem Cells/cytology/*enzymology
MH  - Humans
MH  - Stem Cells/cytology/*enzymology
MH  - Telomerase/*metabolism
MH  - Transcription, Genetic
MH  - Transfection
OTO - NOTNLM
OT  - HMGB1
OT  - hESCs
OT  - neuroectodermal cells
OT  - telomeres
EDAT- 2019/10/30 06:00
MHDA- 2020/06/09 06:00
CRDT- 2019/10/30 06:00
PHST- 2019/10/30 06:00 [pubmed]
PHST- 2020/06/09 06:00 [medline]
PHST- 2019/10/30 06:00 [entrez]
AID - 10.1096/fj.201901465RRR [doi]
PST - ppublish
SO  - FASEB J. 2019 Dec 1;33(12):14307-14324. doi: 10.1096/fj.201901465RRR. Epub 2019 
      Oct 26.