PMID- 30906512
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2001-0370 (Print)
IS  - 2001-0370 (Electronic)
IS  - 2001-0370 (Linking)
VI  - 17
DP  - 2019
TI  - Distinct APE1 Activities Affect the Regulation of VEGF Transcription Under 
      Hypoxic Conditions.
PG  - 324-332
LID - 10.1016/j.csbj.2019.02.007 [doi]
AB  - Angiogenesis is essential for tumor growth. Vascular endothelial growth factor 
      (VEGF), a crucial factor in tumor angiogenesis, has been reported to be 
      transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1). An 8-oxo-G or 
      apurinic/apyrimidinic (AP) site, which is frequently associated with DNA damage, 
      has been identified in the promoter region of VEGF. However, the detailed 
      molecular mechanisms by which AP sites regulate VEGF gene transcription are 
      largely unknown. The dual functional protein apurinic/apyrimidinic endonuclease 1 
      (APE1) is both the key enzyme in DNA base excision repair and the redox factor 
      shown to regulate HIF-1 DNA-binding activity. In the present study, we tested the 
      involvement of both the AP endonuclease and redox activity of APE1 in regulating 
      HIF-1 DNA binding and VEGF transcription in HUVECs. By employing two APE1 
      activity-specific inhibitors and AP-site-containing reporter constructs, we 
      confirmed that both activities of APE1 were involved in regulating VEGF 
      expression under hypoxic conditions. Furthermore, we found that the interaction 
      between APE1 and its downstream repair enzyme, DNA polymerase beta, was compromised 
      when the N-terminal structure of APE1 was distorted under oxidative conditions. 
      Our data suggest that the DNA repair and redox activity of APE1 can play a 
      collaborative role in regulating the transcriptional initiation of the 
      AP-site-containing promoter.
FAU - Li, Mengxia
AU  - Li M
AD  - Cancer Center, The Third Affiliated Hospital and Research Institute of Surgery of 
      Army Medical University (Third Military Medical University), Chongqing 400042, PR 
      China.
FAU - Dai, Nan
AU  - Dai N
AD  - Cancer Center, The Third Affiliated Hospital and Research Institute of Surgery of 
      Army Medical University (Third Military Medical University), Chongqing 400042, PR 
      China.
FAU - Wang, Dong
AU  - Wang D
AD  - Cancer Center, The Third Affiliated Hospital and Research Institute of Surgery of 
      Army Medical University (Third Military Medical University), Chongqing 400042, PR 
      China.
FAU - Zhong, Zhaoyang
AU  - Zhong Z
AD  - Cancer Center, The Third Affiliated Hospital and Research Institute of Surgery of 
      Army Medical University (Third Military Medical University), Chongqing 400042, PR 
      China.
LA  - eng
PT  - Journal Article
DEP - 20190221
PL  - Netherlands
TA  - Comput Struct Biotechnol J
JT  - Computational and structural biotechnology journal
JID - 101585369
PMC - PMC6411614
OTO - NOTNLM
OT  - AP site
OT  - AP sites, Apurinic/apyrimidinic sites
OT  - APE1
OT  - APE1, Apurinic/apyrimidinic endonuclease
OT  - BER, Base excision repair
OT  - Co-IP, Coimmunoprecipitation
OT  - EMSA, Electrophoretic mobility-shift assay
OT  - Egr-1, Early growth response protein-1
OT  - Fapy, Formamidopyrimidine
OT  - HIF-1
OT  - HIF-1, Hypoxia-induced factor-1
OT  - HRE, Hypoxic response element
OT  - HUVEC, Human umbilical vein endothelial cells
OT  - Hypoxia
OT  - NF-kappaB, Nuclear factor-kappa B
OT  - OGG1, DNA Oxoguanine glycosylase 1
OT  - Pol beta, DNA Polymerase beta
OT  - Redox
OT  - VEGF, Vascular endothelial growth factor
OT  - qPCR, Quantitative PCR
EDAT- 2019/03/25 06:00
MHDA- 2019/03/25 06:01
PMCR- 2019/02/21
CRDT- 2019/03/26 06:00
PHST- 2018/11/05 00:00 [received]
PHST- 2019/02/14 00:00 [revised]
PHST- 2019/02/15 00:00 [accepted]
PHST- 2019/03/26 06:00 [entrez]
PHST- 2019/03/25 06:00 [pubmed]
PHST- 2019/03/25 06:01 [medline]
PHST- 2019/02/21 00:00 [pmc-release]
AID - S2001-0370(18)30237-X [pii]
AID - 10.1016/j.csbj.2019.02.007 [doi]
PST - epublish
SO  - Comput Struct Biotechnol J. 2019 Feb 21;17:324-332. doi: 
      10.1016/j.csbj.2019.02.007. eCollection 2019.