The role of SCF Skp2 and SCF β-TrCP1/2 in the cerebellar granule cell precursors.

Autor: Yamashita M; Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan., Owa T; Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan., Shiraishi R; Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan.; Department of NCNP Brain Function and Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, TMDU, Tokyo, Japan., Adachi T; Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan.; Department of Life Science and Medical Bioscience, Graduate School of Advance Science and Engineering, TWIns, Waseda University, Tokyo, Japan., Ichijo K; Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan.; Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan., Taya S; Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan., Miyashita S; Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan., Hoshino M; Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Genes to cells : devoted to molecular & cellular mechanisms [Genes Cells] 2020 Dec; Vol. 25 (12), pp. 796-810. Date of Electronic Publication: 2020 Nov 23.
DOI: 10.1111/gtc.12813
Abstrakt: A proper balance between proliferation and differentiation of cerebellar granule cell precursors (GCPs) is required for appropriate cerebellar morphogenesis. The Skp1-Cullin1-F-box (SCF) complex, an E3 ubiquitin ligase complex, is involved in polyubiquitination and subsequent degradation of various cell cycle regulators and transcription factors. However, it remains unknown how the SCF complex affects proliferation and differentiation of GCPs. In this study, we found that the scaffold protein Cullin1, and F-box proteins Skp2, β-TrCP1 and β-TrCP2 are expressed in the external granule layer (EGL). Knockdown of these molecules in the EGL showed that Cullin1, Skp2 and β-TrCP2 enhanced differentiation of GCPs. We also observed accumulation of cyclin-dependent kinase inhibitor p27 in GCPs when treated with a Cullin1 inhibitor or proteasome inhibitor. Furthermore, knockdown of p27 rescued enhancement of differentiation by Cullin1 knockdown. These results suggest that the SCF complex is involved in the maintenance of the proliferative state of GCPs through p27 degradation. In addition, inhibition of Cullin1 activity also prevented cell proliferation and enhanced accumulation of p27 in Daoy cells, a cell line derived from the sonic hedgehog subtype of medulloblastoma. This suggested that excess degradation of p27 through the SCF complex causes overproliferation of medulloblastoma cells.
(© 2020 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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