Proteomics

Dataset Information

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Hexokinase 2 is a transcriptional targetHexokinase 2 is a transcriptional target and a positive modulator of AHR signalling and a positive modulator of AHR signalling


ABSTRACT: The Aryl Hydrocarbon Receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanistically achieved remains poorly understood. We show that Hexokinase 2 (HK2) a metabolic enzyme fuelling cancer cell growth, is a transcriptional target of AHR as well as a modulator of its activity. Expression of HK2 is positively regulated by AHR upon exposure to agonists both in human cells and in mice lung tissues. Conversely, over-expression of HK2 regulates the abundance of many proteins involved in the regulation of AHR signalling and these changes are linked with altered AHR expression levels and transcriptional activity. HK2 expression also shows a negative correlation with AHR promoter methylation in tumours, and these tumours with high HK2 expression and low AHR methylation are associated with a worse overall survival in patients. In sum, our study provides novel insights into how AHR signalling is regulated which may help our understanding of the context-specific effects of this pathway and may have implications in cancer.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

SUBMITTER: Benoit Miotto  

LAB HEAD: Benoit Miotto

PROVIDER: PXD028992 | Pride | 2022-05-31

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
BeMI180608_U2OS-HK2_2_SCX2_Q26773.raw Raw
BeMI180608_U2OS_1_SCX1_Q26742.raw Raw
BeMI180608_U2OS_1_SCX2_Q26743.raw Raw
BeMI180608_U2OS_1_SCX3_Q26744.raw Raw
BeMI180608_U2OS_1_SCX4_Q26745.raw Raw
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Publications

Hexokinase 2 is a transcriptional target and a positive modulator of AHR signalling.

Watzky Manon M   Huard Solène S   Juricek Ludmila L   Dairou Julien J   Chauvet Caroline C   Coumoul Xavier X   Letessier Anne A   Miotto Benoit B  

Nucleic acids research 20220601 10


The aryl hydrocarbon receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanistically achieved remains poorly understood. We show that hexokinase 2 (HK2) a metabolic enzyme fuelling cancer cell growth, is a transcriptional target of AHR as well as a modulator of its activity. Expression o  ...[more]

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