Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics*
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Blotting, Western
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Cells, Cultured
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Chromatin Immunoprecipitation
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Electrophoretic Mobility Shift Assay
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Embryo, Mammalian / cytology
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Embryo, Mammalian / metabolism
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Gene Expression Regulation, Neoplastic*
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Humans
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Mice
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Neoplasm Proteins / genetics*
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Neoplasms / genetics
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Neoplasms / metabolism
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Neoplasms / pathology
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Phosphorylation
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Promoter Regions, Genetic / genetics*
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Protein Binding
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Regulatory Sequences, Nucleic Acid
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction*
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Smad Proteins / antagonists & inhibitors
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Smad Proteins / genetics
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Smad Proteins / metabolism*
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Transcriptional Activation*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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NUPR1 protein, human
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Neoplasm Proteins
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RNA, Messenger
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RNA, Small Interfering
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Smad Proteins
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Transforming Growth Factor beta