PMID- 30272821
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20200330
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 234
IP  - 5
DP  - 2019 May
TI  - Mutant p53(R248Q) downregulates oxidative phosphorylation and upregulates 
      glycolysis under normoxia and hypoxia in human cervix cancer cells.
PG  - 5524-5536
LID - 10.1002/jcp.27354 [doi]
AB  - Mutations in p53 are strongly associated with several highly malignant cancer 
      phenotypes but its role in regulating energy metabolism has not been completely 
      elucidated. The effect on glycolysis and oxidative phosphorylation (OxPhos) of 
      mutant p53(R248Q) overexpression in HeLa cells (HeLa-M) was analyzed and compared 
      with cells overexpressing wild-type p53 (HeLa-H) and nontransfected cells 
      containing negligible p53 levels (HeLa-L). p53 (R248Q) overexpression induced 
      early cell detachment during in vitro growth; however, detached HeLa-M cells 
      showed high viability, shorter generation time and significant diminution in the 
      adhesion proteins E-cadherin and beta-catenin versus HeLa-H and HeLa-L cells. Under 
      normoxia, a lower growth rate of attached HeLa-M cells correlated with decreased 
      levels of proliferating cell nuclear antigen (PCNA), peroxisome 
      proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha), adenosine 
      monophosphate-activated protein kinase (AMPK), mitochondrial proteins (20-80%) 
      and OxPhos flux (69 +/- 12%). On the contrary, HeLa-M also showed increased 
      contents of CDKN1A, nuclear factor kappaB (NF-kappaB), c-MYC, hypoxia-inducible factor 
      1-alpha (HIF-1alpha; 1-4 times), glycolytic HIF-1alpha targets (2-4 times), and glycolysis 
      flux (2-fold) versus HeLa-H. In consequence, glycolysis provided ~70% of the 
      cellular adenosine triphosphate (ATP) in HeLa-M cells under normoxia whereas, 
      OxPhos predominated (65-82%) in HeLa-H and HeLa-L cells. Pifithrin-alpha, a specific 
      p53 inhibitor, did not alter the p53 (R248Q) target protein contents and OxPhos 
      and glycolytic fluxes, and a poor HIF-1alpha-p53 (R248Q) interaction was attained, in 
      HeLa-M cells. These observations suggested that p53 (R248Q) deficiently 
      interacted with pifithrin-alpha and HIF-1alpha. Therefore, lower mitochondrial 
      biogenesis, deficient HIF-1alpha/mutant p53 interaction, and development of a 
      pseudohypoxic state under normoxia were the apparent biochemical mechanisms 
      underlying glycolysis activation and OxPhos downregulation in HeLa-M cells.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Hernandez-Resendiz, Ileana
AU  - Hernandez-Resendiz I
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Gallardo-Perez, Juan Carlos
AU  - Gallardo-Perez JC
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Lopez-Macay, Ambar
AU  - Lopez-Macay A
AD  - Laboratorio de Enfermedades Neuromusculares, Instituto Nacional de 
      Rehabilitacion, Ciudad de Mexico, Mexico.
FAU - Robledo-Cadena, Diana Xochiquetzal
AU  - Robledo-Cadena DX
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Garcia-Villa, Enrique
AU  - Garcia-Villa E
AD  - Laboratorio de Biologia y Genetica Molecular, Centro de Investigacion y de 
      Estudios Avanzados del Instituto Politecnico Nacional-Zacatenco, Ciudad de 
      Mexico, Mexico.
FAU - Gariglio, Patricio
AU  - Gariglio P
AD  - Laboratorio de Biologia y Genetica Molecular, Centro de Investigacion y de 
      Estudios Avanzados del Instituto Politecnico Nacional-Zacatenco, Ciudad de 
      Mexico, Mexico.
FAU - Saavedra, Emma
AU  - Saavedra E
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Moreno-Sanchez, Rafael
AU  - Moreno-Sanchez R
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
FAU - Rodriguez-Enriquez, Sara
AU  - Rodriguez-Enriquez S
AUID- ORCID: 0000-0002-0822-1233
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Ciudad de Mexico, 
      Mexico.
AD  - Laboratorio de Medicina Translacional, Instituto Nacional de Cancerologia, Ciudad 
      de Mexico, Mexico.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180910
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Cell Proliferation
MH  - Female
MH  - *Glycolysis
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Mitochondria/genetics/metabolism/pathology
MH  - *Mutation
MH  - Organelle Biogenesis
MH  - *Oxidative Phosphorylation
MH  - Tumor Hypoxia
MH  - Tumor Microenvironment
MH  - Tumor Suppressor Protein p53/*genetics/metabolism
MH  - Uterine Cervical Neoplasms/*genetics/*metabolism/pathology
OTO - NOTNLM
OT  - cancer cells
OT  - glycolysis
OT  - mutant p53
OT  - oxidative phosphorylation
EDAT- 2018/10/03 06:00
MHDA- 2020/03/31 06:00
CRDT- 2018/10/02 06:00
PHST- 2017/12/08 00:00 [received]
PHST- 2018/08/17 00:00 [accepted]
PHST- 2018/10/03 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
PHST- 2018/10/02 06:00 [entrez]
AID - 10.1002/jcp.27354 [doi]
PST - ppublish
SO  - J Cell Physiol. 2019 May;234(5):5524-5536. doi: 10.1002/jcp.27354. Epub 2018 Sep 
      10.