Functional whole-genome analysis identifies polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator αB-crystallin

Cristina Draghetti, Catherine Salvat, Francisca Zanoguera, Marie Laure Curchod, Chloé Vignaud, Helene Peixoto, Alessandro Di Cara, David Fischer, Mohanraj Dhanabal, Goutopoulos Andreas, Hadi Abderrahim, Christian Rommel, Montserrat Camps

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

This study aimed at identifying transcriptional changes associated to neuronal differentiation induced by six distinct stimuli using whole-genome microarray hybridization analysis. Bioinformatics analyses revealed the clustering of these six stimuli into two categories, suggesting separate gene/pathway dependence. Treatment with specific inhibitors demonstrated the requirement of both Janus kinase and microtubule-associated protein kinase activation to trigger differentiation with nerve growth factor (NGF) and dibutyryl cAMP. Conversely, activation of protein kinase A, phosphatidylinositol-3-kinase α, and mammalian target of rapamycin, although required for dibutyryl cAMP-induced differentiation, exerted a negative feedback on NGF-induced differentiation. We identified Polo-like kinase 2 (Plk2) and poliovirus receptor (PVR) as indispensable for NGF-driven neuronal differentiation αB-crystallin (Cryab) as an inhibitor of this process. Silencing of Plk2 or PVR blocked NGF-triggered differentiation and Cryab down-regulation, while silencing of Cryab enhanced NGF-induced differentiation. Our results position both Plk2 and PVR upstream of the negative regulator Cryab in the pathway(s) leading to neuronal differentiation triggered by NGF.

Original languageEnglish
Pages (from-to)32053-32065
Number of pages13
JournalJournal of Biological Chemistry
Volume284
Issue number46
DOIs
Publication statusPublished - 30 Nov 2009
Externally publishedYes

Fingerprint

Crystallins
Nerve Growth Factor
Phosphotransferases
Genes
Genome
Chemical activation
Phosphatidylinositol 3-Kinase
Janus Kinases
Microtubule-Associated Proteins
Sirolimus
Microarray Analysis
Bioinformatics
Microarrays
Cyclic AMP-Dependent Protein Kinases
Computational Biology
Protein Kinases
Cluster Analysis
poliovirus receptor
Down-Regulation
Feedback

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Functional whole-genome analysis identifies polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator αB-crystallin. / Draghetti, Cristina; Salvat, Catherine; Zanoguera, Francisca; Curchod, Marie Laure; Vignaud, Chloé; Peixoto, Helene; Di Cara, Alessandro; Fischer, David; Dhanabal, Mohanraj; Andreas, Goutopoulos; Abderrahim, Hadi; Rommel, Christian; Camps, Montserrat.

In: Journal of Biological Chemistry, Vol. 284, No. 46, 30.11.2009, p. 32053-32065.

Research output: Contribution to journalArticle

Draghetti, C, Salvat, C, Zanoguera, F, Curchod, ML, Vignaud, C, Peixoto, H, Di Cara, A, Fischer, D, Dhanabal, M, Andreas, G, Abderrahim, H, Rommel, C & Camps, M 2009, 'Functional whole-genome analysis identifies polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator αB-crystallin', Journal of Biological Chemistry, vol. 284, no. 46, pp. 32053-32065. https://doi.org/10.1074/jbc.M109.009324
Draghetti, Cristina ; Salvat, Catherine ; Zanoguera, Francisca ; Curchod, Marie Laure ; Vignaud, Chloé ; Peixoto, Helene ; Di Cara, Alessandro ; Fischer, David ; Dhanabal, Mohanraj ; Andreas, Goutopoulos ; Abderrahim, Hadi ; Rommel, Christian ; Camps, Montserrat. / Functional whole-genome analysis identifies polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator αB-crystallin. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 46. pp. 32053-32065.
@article{09133f50aed64ff8aa545b8a9d38f600,
title = "Functional whole-genome analysis identifies polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator αB-crystallin",
abstract = "This study aimed at identifying transcriptional changes associated to neuronal differentiation induced by six distinct stimuli using whole-genome microarray hybridization analysis. Bioinformatics analyses revealed the clustering of these six stimuli into two categories, suggesting separate gene/pathway dependence. Treatment with specific inhibitors demonstrated the requirement of both Janus kinase and microtubule-associated protein kinase activation to trigger differentiation with nerve growth factor (NGF) and dibutyryl cAMP. Conversely, activation of protein kinase A, phosphatidylinositol-3-kinase α, and mammalian target of rapamycin, although required for dibutyryl cAMP-induced differentiation, exerted a negative feedback on NGF-induced differentiation. We identified Polo-like kinase 2 (Plk2) and poliovirus receptor (PVR) as indispensable for NGF-driven neuronal differentiation αB-crystallin (Cryab) as an inhibitor of this process. Silencing of Plk2 or PVR blocked NGF-triggered differentiation and Cryab down-regulation, while silencing of Cryab enhanced NGF-induced differentiation. Our results position both Plk2 and PVR upstream of the negative regulator Cryab in the pathway(s) leading to neuronal differentiation triggered by NGF.",
author = "Cristina Draghetti and Catherine Salvat and Francisca Zanoguera and Curchod, {Marie Laure} and Chlo{\'e} Vignaud and Helene Peixoto and {Di Cara}, Alessandro and David Fischer and Mohanraj Dhanabal and Goutopoulos Andreas and Hadi Abderrahim and Christian Rommel and Montserrat Camps",
year = "2009",
month = "11",
day = "30",
doi = "10.1074/jbc.M109.009324",
language = "English",
volume = "284",
pages = "32053--32065",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "46",

}

TY - JOUR

T1 - Functional whole-genome analysis identifies polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator αB-crystallin

AU - Draghetti, Cristina

AU - Salvat, Catherine

AU - Zanoguera, Francisca

AU - Curchod, Marie Laure

AU - Vignaud, Chloé

AU - Peixoto, Helene

AU - Di Cara, Alessandro

AU - Fischer, David

AU - Dhanabal, Mohanraj

AU - Andreas, Goutopoulos

AU - Abderrahim, Hadi

AU - Rommel, Christian

AU - Camps, Montserrat

PY - 2009/11/30

Y1 - 2009/11/30

N2 - This study aimed at identifying transcriptional changes associated to neuronal differentiation induced by six distinct stimuli using whole-genome microarray hybridization analysis. Bioinformatics analyses revealed the clustering of these six stimuli into two categories, suggesting separate gene/pathway dependence. Treatment with specific inhibitors demonstrated the requirement of both Janus kinase and microtubule-associated protein kinase activation to trigger differentiation with nerve growth factor (NGF) and dibutyryl cAMP. Conversely, activation of protein kinase A, phosphatidylinositol-3-kinase α, and mammalian target of rapamycin, although required for dibutyryl cAMP-induced differentiation, exerted a negative feedback on NGF-induced differentiation. We identified Polo-like kinase 2 (Plk2) and poliovirus receptor (PVR) as indispensable for NGF-driven neuronal differentiation αB-crystallin (Cryab) as an inhibitor of this process. Silencing of Plk2 or PVR blocked NGF-triggered differentiation and Cryab down-regulation, while silencing of Cryab enhanced NGF-induced differentiation. Our results position both Plk2 and PVR upstream of the negative regulator Cryab in the pathway(s) leading to neuronal differentiation triggered by NGF.

AB - This study aimed at identifying transcriptional changes associated to neuronal differentiation induced by six distinct stimuli using whole-genome microarray hybridization analysis. Bioinformatics analyses revealed the clustering of these six stimuli into two categories, suggesting separate gene/pathway dependence. Treatment with specific inhibitors demonstrated the requirement of both Janus kinase and microtubule-associated protein kinase activation to trigger differentiation with nerve growth factor (NGF) and dibutyryl cAMP. Conversely, activation of protein kinase A, phosphatidylinositol-3-kinase α, and mammalian target of rapamycin, although required for dibutyryl cAMP-induced differentiation, exerted a negative feedback on NGF-induced differentiation. We identified Polo-like kinase 2 (Plk2) and poliovirus receptor (PVR) as indispensable for NGF-driven neuronal differentiation αB-crystallin (Cryab) as an inhibitor of this process. Silencing of Plk2 or PVR blocked NGF-triggered differentiation and Cryab down-regulation, while silencing of Cryab enhanced NGF-induced differentiation. Our results position both Plk2 and PVR upstream of the negative regulator Cryab in the pathway(s) leading to neuronal differentiation triggered by NGF.

UR - http://www.scopus.com/inward/record.url?scp=70450230349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70450230349&partnerID=8YFLogxK

U2 - 10.1074/jbc.M109.009324

DO - 10.1074/jbc.M109.009324

M3 - Article

C2 - 19700763

AN - SCOPUS:70450230349

VL - 284

SP - 32053

EP - 32065

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 46

ER -