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IGF-1R nuclear import and recruitment to chromatin involves both alpha and beta subunits.

ABSTRACT: Mature type 1 insulin-like growth factor receptors (IGF-1Rs) are heterotetrameric structures comprising two extracellular α-subunits disulphide-bonded to two transmembrane β-subunits with tyrosine kinase activity. IGF-1R is a well-known cell surface mediator of malignant growth, with an incompletely understood role upon nuclear import as a transcriptional regulator. Previous characterisation of nuclear IGF-1R focused on IGF-1Rβ. Here, we aimed to clarify the source of nuclear IGF-1R and investigate whether α-subunits contribute to nuclear IGF-1R function. Using prostate cancer cell lines DU145 and 22Rv1 we detected nuclear α- and β-subunits, with increase in nuclear signal upon IGF-treatment and reduction in response to IGF-1R inhibitor BMS-754807. Following biotinylation of cell surface proteins, biotinylated α- and β-subunits were detected in nuclear extracts of both cell lines. Furthermore, α- and β-subunits reciprocally co-precipitated from nuclear extract. Finally, we detected recruitment of both subunits to regulatory regions of chromatin, including the promoter of the oncogene JUN, that we previously identified in ChIP-seq as sites of IGF-1Rβ enrichment. These data confirm the cell surface origin of nuclear IGF-1R, suggest the presence of nuclear αβ complexes and reveal that both IGF-1Rα- and β-subunits contribute to pro-tumorigenic functions of nuclear IGF-1R.

Supplementary information

The online version contains supplementary material available at 10.1007/s12672-021-00407-8.

SUBMITTER: Mills JV

PROVIDER: S-EPMC8084799 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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IGF-1R nuclear import and recruitment to chromatin involves both alpha and beta subunits.

Mills Jack V JV Osher Eliot E Rieunier Guillaume G Mills Ian G IG Macaulay Valentine M VM

Discover oncology 20210429 1

Mature type 1 insulin-like growth factor receptors (IGF-1Rs) are heterotetrameric structures comprising two extracellular α-subunits disulphide-bonded to two transmembrane β-subunits with tyrosine kinase activity. IGF-1R is a well-known cell surface mediator of malignant growth, with an incompletely understood role upon nuclear import as a transcriptional regulator. Previous characterisation of nuclear IGF-1R focused on IGF-1Rβ. Here, we aimed to clarify the source of nuclear IGF-1R and investig ...[more]

PMID: 33969359

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Dataset Information

IGF-1R nuclear import and recruitment to chromatin involves both alpha and beta subunits.

Supplementary information

Publications

IGF-1R nuclear import and recruitment to chromatin involves both alpha and beta subunits.

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