The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action

Audrey Griveau, G Devailly, L Eberst, N Navaratnam, B Le Calvé, Mylène Ferrand, P Faull, Arnaud Augert, R Dante, J M Vanacker, David Vindrieux, D. Bernard

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Little is known about the biological role of the phospholipase A2 receptor (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an important role in regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are largely undeciphered. In this study, we observed that PLA2R1 increases the mitochondrial content, judged by increased levels of numerous mitochondrial proteins, of the mitochondrial structural component cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA replication and transcription factor TFAM. This effect of PLA2R1 relies on a transcriptional program controlled by the estrogen-related receptor alpha1 (ERRα) mitochondrial master regulator. Expression of ERRα and of its nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic expression, and this effect is mediated by JAK2. Conversely, downregulation of PLA2R1 decreases the level of ERRα and of its nucleus-encoded mitochondrial targets. Finally, blocking the ERRα-controlled mitochondrial program largely inhibits the PLA2R1-induced tumor-suppressive response. Together, our data document ERRα and its mitochondrial program as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.

langue originaleAnglais
Pages (de - à)5033-42
Nombre de pages10
journalOncogene
Volume35
Numéro de publication38
Les DOIs
étatPublié - 2016
Modification externeOui

Empreinte digitale

Estrogen Receptors
Up-Regulation
Neoplasms
Mitochondrial DNA
Phospholipase A2 Receptors
Cardiolipins
Mitochondrial Proteins
DNA Replication
Transcription Factors
Down-Regulation
Proteins

Citer ceci

Griveau, A., Devailly, G., Eberst, L., Navaratnam, N., Le Calvé, B., Ferrand, M., ... Bernard, D. (2016). The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action. Oncogene, 35(38), 5033-42. https://doi.org/10.1038/onc.2016.43
Griveau, Audrey ; Devailly, G ; Eberst, L ; Navaratnam, N ; Le Calvé, B ; Ferrand, Mylène ; Faull, P ; Augert, Arnaud ; Dante, R ; Vanacker, J M ; Vindrieux, David ; Bernard, D. . / The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action. Dans: Oncogene. 2016 ; Vol 35, Numéro 38. p. 5033-42.
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abstract = "Little is known about the biological role of the phospholipase A2 receptor (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an important role in regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are largely undeciphered. In this study, we observed that PLA2R1 increases the mitochondrial content, judged by increased levels of numerous mitochondrial proteins, of the mitochondrial structural component cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA replication and transcription factor TFAM. This effect of PLA2R1 relies on a transcriptional program controlled by the estrogen-related receptor alpha1 (ERRα) mitochondrial master regulator. Expression of ERRα and of its nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic expression, and this effect is mediated by JAK2. Conversely, downregulation of PLA2R1 decreases the level of ERRα and of its nucleus-encoded mitochondrial targets. Finally, blocking the ERRα-controlled mitochondrial program largely inhibits the PLA2R1-induced tumor-suppressive response. Together, our data document ERRα and its mitochondrial program as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.",
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Griveau, A, Devailly, G, Eberst, L, Navaratnam, N, Le Calvé, B, Ferrand, M, Faull, P, Augert, A, Dante, R, Vanacker, JM, Vindrieux, D & Bernard, D 2016, 'The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action', Oncogene, VOL. 35, Numéro 38, p. 5033-42. https://doi.org/10.1038/onc.2016.43

The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action. / Griveau, Audrey; Devailly, G; Eberst, L; Navaratnam, N; Le Calvé, B; Ferrand, Mylène; Faull, P; Augert, Arnaud; Dante, R; Vanacker, J M; Vindrieux, David; Bernard, D. .

Dans: Oncogene, Vol 35, Numéro 38, 2016, p. 5033-42.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action

AU - Griveau, Audrey

AU - Devailly, G

AU - Eberst, L

AU - Navaratnam, N

AU - Le Calvé, B

AU - Ferrand, Mylène

AU - Faull, P

AU - Augert, Arnaud

AU - Dante, R

AU - Vanacker, J M

AU - Vindrieux, David

AU - Bernard, D.

PY - 2016

Y1 - 2016

N2 - Little is known about the biological role of the phospholipase A2 receptor (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an important role in regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are largely undeciphered. In this study, we observed that PLA2R1 increases the mitochondrial content, judged by increased levels of numerous mitochondrial proteins, of the mitochondrial structural component cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA replication and transcription factor TFAM. This effect of PLA2R1 relies on a transcriptional program controlled by the estrogen-related receptor alpha1 (ERRα) mitochondrial master regulator. Expression of ERRα and of its nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic expression, and this effect is mediated by JAK2. Conversely, downregulation of PLA2R1 decreases the level of ERRα and of its nucleus-encoded mitochondrial targets. Finally, blocking the ERRα-controlled mitochondrial program largely inhibits the PLA2R1-induced tumor-suppressive response. Together, our data document ERRα and its mitochondrial program as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.

AB - Little is known about the biological role of the phospholipase A2 receptor (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an important role in regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are largely undeciphered. In this study, we observed that PLA2R1 increases the mitochondrial content, judged by increased levels of numerous mitochondrial proteins, of the mitochondrial structural component cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA replication and transcription factor TFAM. This effect of PLA2R1 relies on a transcriptional program controlled by the estrogen-related receptor alpha1 (ERRα) mitochondrial master regulator. Expression of ERRα and of its nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic expression, and this effect is mediated by JAK2. Conversely, downregulation of PLA2R1 decreases the level of ERRα and of its nucleus-encoded mitochondrial targets. Finally, blocking the ERRα-controlled mitochondrial program largely inhibits the PLA2R1-induced tumor-suppressive response. Together, our data document ERRα and its mitochondrial program as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.

KW - Journal Article

U2 - 10.1038/onc.2016.43

DO - 10.1038/onc.2016.43

M3 - Article

C2 - 27041564

VL - 35

SP - 5033

EP - 5042

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 38

ER -