PMID- 37165028
OWN - NLM
STAT- MEDLINE
DCOM- 20230512
LR  - 20230601
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 May 10
TI  - Analysis and functional relevance of the chaperone TRAP-1 interactome in the 
      metabolic regulation and mitochondrial integrity of cancer cells.
PG  - 7584
LID - 10.1038/s41598-023-34728-1 [doi]
LID - 7584
AB  - The 90 kDa heat shock protein, Hsp90, functions as a cancer chaperone 
      contributing to tumor proliferation. We have encountered the mitochondrial 
      homolog of Hsp90, the TRAP-1, regulating mitochondrial dynamics, metabolism, and 
      tumor metastasis. Although Hsp90 is associated with a broad network of proteins 
      regulating various cellular processes, TRAP-1-mediated cellular networks are 
      unclear. Therefore, using TRAP-1 knockdown (KD) and overexpression (OE) systems, 
      we compared their quantitative transcriptome (RNA Sequencing) and proteomic 
      (LC-MS/MS) patterns to obtain molecular signatures that are altered in response 
      to TRAP-1 KD or OE. We report TRAP-1 modulating vital metabolic pathways such as 
      the tricarboxylic acid cycle, oxidative phosphorylation, electron transport 
      chain, glycolysis, and gluconeogenesis. In addition, TRAP-1 facilitated the 
      pentose phosphate pathway to shunt carbons back to glycolysis or gluconeogenesis, 
      a much-solicited tumor response. Subsequently, we examined the TRAP-1 interactome 
      using the tandem affinity purification system and identified 255 unique proteins. 
      These diverse proteins appear to regulate several cellular processes, including 
      energy metabolism, suggesting that TRAP-1, in addition to metabolic rewiring, 
      maintains mitochondrial integrity. Our study exposes the unknown functions of 
      TRAP-1 in cancer cells. Systematic evaluation of TRAP-1 interactors may uncover 
      novel regulatory mechanisms in disease aggression. Since metabolic inhibitors are 
      emerging as potential anticancer agents, our study gains importance.
CI  - (c) 2023. The Author(s).
FAU - Dharaskar, Shrikant Purushottam
AU  - Dharaskar SP
AD  - CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, Telangana, 
      500007, India.
AD  - AcSIR - Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, 
      India.
FAU - Paithankar, Khanderao
AU  - Paithankar K
AD  - CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, Telangana, 
      500007, India.
FAU - Amere Subbarao, Sreedhar
AU  - Amere Subbarao S
AD  - CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, Telangana, 
      500007, India. assr@ccmb.res.in.
AD  - AcSIR - Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, 
      India. assr@ccmb.res.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230510
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Molecular Chaperones)
RN  - 0 (HSP90 Heat-Shock Proteins)
SB  - IM
MH  - Humans
MH  - *Proteomics
MH  - Chromatography, Liquid
MH  - Tandem Mass Spectrometry
MH  - Molecular Chaperones/metabolism
MH  - HSP90 Heat-Shock Proteins/metabolism
MH  - *Neoplasms/genetics
PMC - PMC10172325
COIS- The authors declare no competing interests.
EDAT- 2023/05/11 00:42
MHDA- 2023/05/12 07:06
PMCR- 2023/05/10
CRDT- 2023/05/10 23:19
PHST- 2022/12/05 00:00 [received]
PHST- 2023/05/06 00:00 [accepted]
PHST- 2023/05/12 07:06 [medline]
PHST- 2023/05/11 00:42 [pubmed]
PHST- 2023/05/10 23:19 [entrez]
PHST- 2023/05/10 00:00 [pmc-release]
AID - 10.1038/s41598-023-34728-1 [pii]
AID - 34728 [pii]
AID - 10.1038/s41598-023-34728-1 [doi]
PST - epublish
SO  - Sci Rep. 2023 May 10;13(1):7584. doi: 10.1038/s41598-023-34728-1.