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Current Osteoporosis Reports

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13.04.2019 | Skeletal Development (R Marcucio and J Feng, Section Editors)

Nuclear Fibroblast Growth Factor Receptor Signaling in Skeletal Development and Disease

verfasst von: Creighton T. Tuzon, Diana Rigueur, Amy E. Merrill

Erschienen in: Current Osteoporosis Reports | Ausgabe 3/2019

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Abstract

Purpose of Review

Fibroblast growth factor receptor (FGFR) signaling regulates proliferation and differentiation during development and homeostasis. While membrane-bound FGFRs play a central role in these processes, the function of nuclear FGFRs is also critical. Here, we highlight mechanisms for nuclear FGFR translocation and the effects of nuclear FGFRs on skeletal development and disease.

Recent Findings

Full-length FGFRs, internalized by endocytosis, enter the nucleus through β-importin-dependent mechanisms that recognize the nuclear localization signal within FGFs. Alternatively, soluble FGFR intracellular fragments undergo nuclear translocation following their proteolytic release from the membrane. FGFRs enter the nucleus during the cellular transition between proliferation and differentiation. Once nuclear, FGFRs interact with chromatin remodelers to alter the epigenetic state and transcription of their target genes. Dysregulation of nuclear FGFR is linked to the etiology of congenital skeletal disorders and neoplastic transformation.

Summary

Revealing the activities of nuclear FGFR will advance our understanding of 20 congenital skeletal disorders caused by FGFR mutations, as well as FGFR-related cancers.

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Titel: Nuclear Fibroblast Growth Factor Receptor Signaling in Skeletal Development and Disease
verfasst von: Creighton T. Tuzon
Diana Rigueur
Amy E. Merrill
Publikationsdatum: 13.04.2019
Verlag: Springer US
Erschienen in: Current Osteoporosis Reports / Ausgabe 3/2019
Print ISSN: 1544-1873
Elektronische ISSN: 1544-2241
DOI: https://doi.org/10.1007/s11914-019-00512-2

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Nuclear Fibroblast Growth Factor Receptor Signaling in Skeletal Development and Disease

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