PMID- 38003426
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20231127
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 22
DP  - 2023 Nov 12
TI  - Membrane Localization and Phosphorylation of Indoleamine 2,3-Dioxygenase 2 (IDO2) 
      in A549 Human Lung Adenocarcinoma Cells: First Steps in Exploring Its Signaling 
      Function.
LID - 10.3390/ijms242216236 [doi]
LID - 16236
AB  - Indoleamine 2,3-dioxygenase 2 (IDO2) is a paralog of Indoleamine 2,3-dioxygenase 
      1 (IDO1), a tryptophan-degrading enzyme producing immunomodulatory molecules. 
      However, the two proteins are unlikely to carry out the same functions. IDO2 
      shows little or no tryptophan catabolic activity and exerts contrasting 
      immunomodulatory roles in a context-dependent manner in cancer and autoimmune 
      diseases. The recently described potential non-enzymatic activity of IDO2 has 
      suggested its possible involvement in alternative pathways, resulting in either 
      pro- or anti-inflammatory effects in different models. In a previous study on 
      non-small cell lung cancer (NSCLC) tissues, we found that IDO2 expression 
      revealed at the plasma membrane level of tumor cells was significantly associated 
      with poor prognosis. In this study, the A549 human cell line, basally expressing 
      IDO2, was used as an in vitro model of human lung adenocarcinoma to gain more 
      insights into a possible alternative function of IDO2 different from the 
      catalytic one. In these cells, immunocytochemistry and isopycnic sucrose gradient 
      analyses confirmed the IDO2 protein localization in the cell membrane 
      compartment, and the immunoprecipitation of tyrosine-phosphorylated proteins 
      revealed that kinase activities can target IDO2. The different localization from 
      the cytosolic one and the phosphorylation state are the first indications for the 
      signaling function of IDO2, suggesting that the IDO2 non-enzymatic role in cancer 
      cells is worthy of deeper understanding.
FAU - Suvieri, Chiara
AU  - Suvieri C
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
FAU - De Marchis, Francesca
AU  - De Marchis F
AUID- ORCID: 0000-0002-1561-369X
AD  - Institute of Biosciences and Bioresources, Research Division of Perugia, National 
      Research Council (CNR), 06128 Perugia, Italy.
FAU - Mandarano, Martina
AU  - Mandarano M
AUID- ORCID: 0000-0001-5019-4825
AD  - Section of Anatomic Pathology and Histology, Department of Medicine and Surgery, 
      University of Perugia, 06129 Perugia, Italy.
FAU - Ambrosino, Sara
AU  - Ambrosino S
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
FAU - Rossini, Sofia
AU  - Rossini S
AUID- ORCID: 0000-0001-6429-9425
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
FAU - Mondanelli, Giada
AU  - Mondanelli G
AUID- ORCID: 0000-0002-0798-0465
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
FAU - Gargaro, Marco
AU  - Gargaro M
AUID- ORCID: 0000-0003-0645-9800
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
FAU - Panfili, Eleonora
AU  - Panfili E
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
FAU - Orabona, Ciriana
AU  - Orabona C
AUID- ORCID: 0000-0003-3113-0572
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
FAU - Pallotta, Maria Teresa
AU  - Pallotta MT
AUID- ORCID: 0000-0002-0417-1638
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
FAU - Belladonna, Maria Laura
AU  - Belladonna ML
AUID- ORCID: 0000-0001-6522-0870
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
FAU - Volpi, Claudia
AU  - Volpi C
AUID- ORCID: 0000-0002-3967-7954
AD  - Section of Pharmacology, Department of Medicine and Surgery, University of 
      Perugia, 06129 Perugia, Italy.
LA  - eng
GR  - 23084/Italian Association for Cancer Research/
GR  - PRIN2017-20173EAZ2Z and PRIN2020-2020L45ZW4/Italian Ministry of Education, 
      University, and Research/
PT  - Journal Article
DEP - 20231112
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 8DUH1N11BX (Tryptophan)
SB  - IM
MH  - Humans
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism
MH  - Phosphorylation
MH  - *Carcinoma, Non-Small-Cell Lung
MH  - *Lung Neoplasms
MH  - Tryptophan/metabolism
MH  - *Adenocarcinoma of Lung
PMC - PMC10671178
OTO - NOTNLM
OT  - A549
OT  - IDO2
OT  - lung adenocarcinoma
OT  - membrane localization
OT  - tyrosine phosphorylation
COIS- The authors declare that this research was conducted in the absence of any 
      commercial or financial relationships that could be construed as potential 
      conflicts of interest.
EDAT- 2023/11/25 12:45
MHDA- 2023/11/27 12:42
PMCR- 2023/11/12
CRDT- 2023/11/25 01:16
PHST- 2023/09/18 00:00 [received]
PHST- 2023/11/05 00:00 [revised]
PHST- 2023/11/10 00:00 [accepted]
PHST- 2023/11/27 12:42 [medline]
PHST- 2023/11/25 12:45 [pubmed]
PHST- 2023/11/25 01:16 [entrez]
PHST- 2023/11/12 00:00 [pmc-release]
AID - ijms242216236 [pii]
AID - ijms-24-16236 [pii]
AID - 10.3390/ijms242216236 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Nov 12;24(22):16236. doi: 10.3390/ijms242216236.