PMID- 34506922
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20211214
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 214
DP  - 2021 Nov
TI  - Loss of beta-Arrestins or six Galpha proteins in HEK293 cells caused Warburg effect and 
      prevented progesterone-induced rapid proteasomal degradation of progesterone 
      receptor membrane component 1.
PG  - 105995
LID - S0960-0760(21)00188-6 [pii]
LID - 10.1016/j.jsbmb.2021.105995 [doi]
AB  - Hormonal dysregulation plays a significant role in the metabolic switching during 
      malignant transformation. Progesterone Receptor Membrane Component 1 (PGRMC1) is 
      a single-pass transmembrane receptor activated by the binding of progesterone 
      (P4), a sex hormone. In a previous study, P4 treatment caused rapid (within 30 
      min) induction of aerobic glycolysis in transformed HEK293 cells, a hallmark 
      malignant phenotype known as the Warburg effect. This metabolic reprogramming was 
      associated with the proteasomal degradation of a 70 kilodalton (kDa) PGRMC1. 
      PGRMC1 interacts with a variety of proteins, including G protein-coupled 
      receptors (GPCRs) and P4-PGRMC1 signaling modulates cyclic adenosine 
      monophosphate (cAMP) production. Therefore, we hypothesized that the P4-induced 
      Warburg effect and proteasomal degradation of PGRMC1 involve G proteins and 
      beta-Arrestins (ARRBs). In the present study, we investigated P4-induced aerobic 
      glycolysis, proteasomal degradation of p70 PGRMC1, as well as abundance and 
      subcellular translocation of PGRMC1 along with two key glycolytic enzymes 
      Hexokinase 1 (HK1) and Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) in six Galpha 
      subunit (Gsix) proteins or ARRB1/2-deficient HEK293 cells. Loss of ARRB1/2 or 
      Gsix proteins inhibited P4-induced p70 PGRMC1 degradation but failed to prevent 
      the P4-induced Warburg effect. Also, deficiency of ARRB1/2 or Gsix proteins 
      differentially affected the basal as well as P4-induced abundance and subcellular 
      translocation of PGRMC1, HK1, and GAPDH proteins. Overall, the findings indicate 
      that P4-PGRMC1-mediated metabolic reprogramming in HEK293 cells depends on 
      beta-Arrestins and Galpha proteins suggesting the involvement of an underlying GPCR 
      signal transduction pathway.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Sabbir, Mohammad Golam
AU  - Sabbir MG
AD  - Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface 
      Albrechtsen Research Centre, Winnipeg, MB, R2H 2A6, Canada; Alzo Biosciences 
      Inc., San Diego, USA. Electronic address: sabbir@alzobio.com.
FAU - Inoue, Asuka
AU  - Inoue A
AD  - Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 
      Japan.
FAU - Taylor, Carla G
AU  - Taylor CG
AD  - Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface 
      Albrechtsen Research Centre, Winnipeg, MB, R2H 2A6, Canada; Department of Food 
      and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, R3T 2N2, 
      Canada; Department of Physiology and Pathophysiology, University of Manitoba, 
      Winnipeg, MB, R3E 0J9, Canada.
FAU - Zahradka, Peter
AU  - Zahradka P
AD  - Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface 
      Albrechtsen Research Centre, Winnipeg, MB, R2H 2A6, Canada; Department of Food 
      and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, R3T 2N2, 
      Canada; Department of Physiology and Pathophysiology, University of Manitoba, 
      Winnipeg, MB, R3E 0J9, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210911
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Membrane Proteins)
RN  - 0 (PGRMC1 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (beta-Arrestins)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.1.1 (HK1 protein, human)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Cyclic AMP/metabolism
MH  - HEK293 Cells
MH  - Hexokinase/biosynthesis
MH  - Humans
MH  - Membrane Proteins/biosynthesis/metabolism
MH  - Progesterone/*metabolism
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Transport
MH  - RNA, Small Interfering/metabolism
MH  - Receptors, Progesterone/biosynthesis/metabolism
MH  - Signal Transduction
MH  - beta-Arrestins/*metabolism
OTO - NOTNLM
OT  - G protein
OT  - Hexokinase
OT  - Progesterone
OT  - Progesterone receptor membrane component 1
OT  - Warburg effect
OT  - beta-Arrestin
EDAT- 2021/09/11 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/09/10 20:14
PHST- 2021/05/29 00:00 [received]
PHST- 2021/08/30 00:00 [revised]
PHST- 2021/09/01 00:00 [accepted]
PHST- 2021/09/11 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/09/10 20:14 [entrez]
AID - S0960-0760(21)00188-6 [pii]
AID - 10.1016/j.jsbmb.2021.105995 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2021 Nov;214:105995. doi: 
      10.1016/j.jsbmb.2021.105995. Epub 2021 Sep 11.