The human NUPR1/P8 gene is transcriptionally activated by transforming growth factor β via the SMAD signalling pathway.
NUPR1 (nuclear protein 1), also called P8 (molecular mass 8 kDa) or COM1 (candidate of metastasis 1), is involved in the stress response and in cancer progression. In the present study, we investigated whether human NUPR1 expression was regulated by TGFβ (transforming growth factor β), a secreted polypeptide largely involved in tumorigenesis. We demonstrate that the expression of NUPR1 was activated by TGFβ at the transcriptional level. We show that this activation is mediated by the SMAD proteins, which are transcription factors specifically involved in the signalling of TGFβ superfamily members. NUPR1 promoter analysis reveals the presence of a functional TGFβ-response element binding the SMAD proteins located in the genomic DNA region corresponding to the 5'-UTR (5'-untranslated region). Altogether, the molecular results of the present study, which demonstrate the existence of a TGFβ/SMAD/NUPR1 activation cascade, open the way to consider and investigate further a new mechanism enabling TGFβ to promote tumorigenesis by inducing stress resistance.
Inserm U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, F-13228 cedex 09 Marseille, France.
Roxane M
RM
Pommier
Johann
J
Gout
David F
DF
Vincent
Carla E
CE
Cano
Bastien
B
Kaniewski
Sylvie
S
Martel
Jonathan
J
Rodriguez
Geneviève
G
Fourel
Ulrich
U
Valcourt
Julien C
JC
Marie
Juan L
JL
Iovanna
Laurent
L
Bartholin
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C491643:NUPR1 protein, human