c-Jun regulates phosphoinositide-dependent kinase 1 transcription: Implication for Akt and protein kinase C activities melanoma tumorigenesis
Mutations in N-RAS and B-RAF, which commonly occur in melanomas, result in constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling. Active ERK increases expression and activity of the c-Jun transcription factor, linking ERK...
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paper:paper_00219258_v285_n2_p903_LopezBergami2023-06-08T14:43:30Z c-Jun regulates phosphoinositide-dependent kinase 1 transcription: Implication for Akt and protein kinase C activities melanoma tumorigenesis Extracellular signal-regulated protein kinase Jun N-terminal kinase Melanoma cells Mitogen activated protein kinase Oncogenic activities Phosphoinositide-dependent kinase 1 Protein kinase c activities Transcriptional regulator Tumorigenesis Up-regulation Cell culture Dermatology Enzyme activity Phosphorylation Transcription Transcription factors Oncology phosphoinositide dependent protein kinase 1 protein c jun protein kinase B protein kinase C animal experiment animal model article carcinogenesis controlled study enzyme activity enzyme phosphorylation human human cell melanoma mouse nonhuman priority journal protein function regulatory mechanism transcription regulation tumor growth upregulation Animals Cell Line, Tumor Extracellular Signal-Regulated MAP Kinases Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System Melanoma Mice Mice, Nude Neoplasm Transplantation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-jun Transcription, Genetic Transplantation, Heterologous Mus Mutations in N-RAS and B-RAF, which commonly occur in melanomas, result in constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling. Active ERK increases expression and activity of the c-Jun transcription factor, linking ERK and Jun N-terminal kinase (JNK) cascades. Here, we show that c-Jun regulates transcription of phosphoinositide-dependent kinase 1 (PDK1) with a concomitant impact on Akt and protein kinase C (PKC) activity and related substrates. Inhibition of c-Jun reduces PDK1 expression and attenuates Akt and PKC activity, which can be restored by exogenous PDK1. c-Jun regulation of PDK1 in melanoma contributes to growth rate and the ability to form tumors in mice. Correspondingly, increased levels of c-Jun in melanoma cell lines coincide with up-regulation of PDK1 and phosphorylation of PKC and Akt. The identification of c-Jun as a transcriptional regulator of PDK1 expression highlights key mechanisms underlying c-Jun oncogenic activity, and provides new insight into the nature of up-regulated Akt and PKC in melanoma. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v285_n2_p903_LopezBergami http://hdl.handle.net/20.500.12110/paper_00219258_v285_n2_p903_LopezBergami |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Extracellular signal-regulated protein kinase Jun N-terminal kinase Melanoma cells Mitogen activated protein kinase Oncogenic activities Phosphoinositide-dependent kinase 1 Protein kinase c activities Transcriptional regulator Tumorigenesis Up-regulation Cell culture Dermatology Enzyme activity Phosphorylation Transcription Transcription factors Oncology phosphoinositide dependent protein kinase 1 protein c jun protein kinase B protein kinase C animal experiment animal model article carcinogenesis controlled study enzyme activity enzyme phosphorylation human human cell melanoma mouse nonhuman priority journal protein function regulatory mechanism transcription regulation tumor growth upregulation Animals Cell Line, Tumor Extracellular Signal-Regulated MAP Kinases Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System Melanoma Mice Mice, Nude Neoplasm Transplantation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-jun Transcription, Genetic Transplantation, Heterologous Mus |
spellingShingle |
Extracellular signal-regulated protein kinase Jun N-terminal kinase Melanoma cells Mitogen activated protein kinase Oncogenic activities Phosphoinositide-dependent kinase 1 Protein kinase c activities Transcriptional regulator Tumorigenesis Up-regulation Cell culture Dermatology Enzyme activity Phosphorylation Transcription Transcription factors Oncology phosphoinositide dependent protein kinase 1 protein c jun protein kinase B protein kinase C animal experiment animal model article carcinogenesis controlled study enzyme activity enzyme phosphorylation human human cell melanoma mouse nonhuman priority journal protein function regulatory mechanism transcription regulation tumor growth upregulation Animals Cell Line, Tumor Extracellular Signal-Regulated MAP Kinases Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System Melanoma Mice Mice, Nude Neoplasm Transplantation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-jun Transcription, Genetic Transplantation, Heterologous Mus c-Jun regulates phosphoinositide-dependent kinase 1 transcription: Implication for Akt and protein kinase C activities melanoma tumorigenesis |
topic_facet |
Extracellular signal-regulated protein kinase Jun N-terminal kinase Melanoma cells Mitogen activated protein kinase Oncogenic activities Phosphoinositide-dependent kinase 1 Protein kinase c activities Transcriptional regulator Tumorigenesis Up-regulation Cell culture Dermatology Enzyme activity Phosphorylation Transcription Transcription factors Oncology phosphoinositide dependent protein kinase 1 protein c jun protein kinase B protein kinase C animal experiment animal model article carcinogenesis controlled study enzyme activity enzyme phosphorylation human human cell melanoma mouse nonhuman priority journal protein function regulatory mechanism transcription regulation tumor growth upregulation Animals Cell Line, Tumor Extracellular Signal-Regulated MAP Kinases Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System Melanoma Mice Mice, Nude Neoplasm Transplantation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-jun Transcription, Genetic Transplantation, Heterologous Mus |
description |
Mutations in N-RAS and B-RAF, which commonly occur in melanomas, result in constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling. Active ERK increases expression and activity of the c-Jun transcription factor, linking ERK and Jun N-terminal kinase (JNK) cascades. Here, we show that c-Jun regulates transcription of phosphoinositide-dependent kinase 1 (PDK1) with a concomitant impact on Akt and protein kinase C (PKC) activity and related substrates. Inhibition of c-Jun reduces PDK1 expression and attenuates Akt and PKC activity, which can be restored by exogenous PDK1. c-Jun regulation of PDK1 in melanoma contributes to growth rate and the ability to form tumors in mice. Correspondingly, increased levels of c-Jun in melanoma cell lines coincide with up-regulation of PDK1 and phosphorylation of PKC and Akt. The identification of c-Jun as a transcriptional regulator of PDK1 expression highlights key mechanisms underlying c-Jun oncogenic activity, and provides new insight into the nature of up-regulated Akt and PKC in melanoma. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. |
title |
c-Jun regulates phosphoinositide-dependent kinase 1 transcription: Implication for Akt and protein kinase C activities melanoma tumorigenesis |
title_short |
c-Jun regulates phosphoinositide-dependent kinase 1 transcription: Implication for Akt and protein kinase C activities melanoma tumorigenesis |
title_full |
c-Jun regulates phosphoinositide-dependent kinase 1 transcription: Implication for Akt and protein kinase C activities melanoma tumorigenesis |
title_fullStr |
c-Jun regulates phosphoinositide-dependent kinase 1 transcription: Implication for Akt and protein kinase C activities melanoma tumorigenesis |
title_full_unstemmed |
c-Jun regulates phosphoinositide-dependent kinase 1 transcription: Implication for Akt and protein kinase C activities melanoma tumorigenesis |
title_sort |
c-jun regulates phosphoinositide-dependent kinase 1 transcription: implication for akt and protein kinase c activities melanoma tumorigenesis |
publishDate |
2010 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v285_n2_p903_LopezBergami http://hdl.handle.net/20.500.12110/paper_00219258_v285_n2_p903_LopezBergami |
_version_ |
1768546239978143744 |