PMID- 31499711
OWN - NLM
STAT- MEDLINE
DCOM- 20200713
LR  - 20200713
IS  - 1551-0018 (Electronic)
IS  - 1547-1063 (Linking)
VI  - 16
IP  - 5
DP  - 2019 Jun 10
TI  - CSB modulates the competition between HIF-1 and p53 upon hypoxia.
PG  - 5247-5262
LID - 10.3934/mbe.2019262 [doi]
AB  - Both hypoxia-inducible factor-1 (HIF-1) and tumor suppressor p53 are involved in 
      the cellular response to hypoxia. It has been reported that HIF-1alpha induces 
      cockayne syndrome B (CSB) to compete with p53 for limited p300. We developed a 
      network model to clarify how the interplay between HIF-1 and p53 modulates 
      cellular output in the presence of CSB. Our results revealed that HIF-1alpha is 
      progressively activated depending on the severity of hypoxia. Activated HIF-1alpha 
      promotes its own activation by inducing CSB to dissociate p300 from p53 under 
      moderate hypoxia; in severe hypoxia, p53 accumulates remarkably due to 
      ATR-dependent phosphorylation and wins the competition for p300. As a result, 
      HIF-1alpha induces PFKL and VEGF to facilitate cellular adaptation to mild and 
      moderate hypoxia respectively, while p53 is activated to induce apoptosis under 
      severe hypoxia. This work may advance the understanding of the modulation of the 
      interplay between HIF-1 and p53 in the hypoxic response.
FAU - Ye, Xiao-Wei
AU  - Ye XW
AD  - National Laboratory of Solid State Microstructures, Department of Physics, and 
      Collaborative Innovation Center of Advanced Microstructures, Nanjing University, 
      Nanjing 210093, P.R. China.
FAU - Zhang, Xiao-Peng
AU  - Zhang XP
AD  - Kuang Yaming Honors School, Nanjing University, Nanjing 210023, P.R. China.
AD  - Institute for Brain Sciences, Nanjing University, Nanjing 210093, P.R. China.
FAU - Liu, Feng
AU  - Liu F
AD  - National Laboratory of Solid State Microstructures, Department of Physics, and 
      Collaborative Innovation Center of Advanced Microstructures, Nanjing University, 
      Nanjing 210093, P.R. China.
AD  - Institute for Brain Sciences, Nanjing University, Nanjing 210093, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Math Biosci Eng
JT  - Mathematical biosciences and engineering : MBE
JID - 101197794
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 3.6.4.- (DNA Helicases)
RN  - EC 3.6.4.12 (ERCC6 protein, human)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - *Apoptosis
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Cell Lineage
MH  - DNA Helicases/*metabolism
MH  - DNA Repair Enzymes/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Oxygen/metabolism
MH  - Phosphorylation
MH  - Poly-ADP-Ribose Binding Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-mdm2/metabolism
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
OTO - NOTNLM
OT  - p53
OT  - CSB
OT  - HIF-1alpha
OT  - hypoxia
OT  - network model
EDAT- 2019/09/11 06:00
MHDA- 2020/07/14 06:00
CRDT- 2019/09/11 06:00
PHST- 2019/09/11 06:00 [entrez]
PHST- 2019/09/11 06:00 [pubmed]
PHST- 2020/07/14 06:00 [medline]
AID - 10.3934/mbe.2019262 [doi]
PST - ppublish
SO  - Math Biosci Eng. 2019 Jun 10;16(5):5247-5262. doi: 10.3934/mbe.2019262.