Reversion of Temperature-Sensitive Mutation by Inhibition of Proteasome-Mediated Degradation of Mutated D123 Protein

Cell Structure and Function

Masumi Ohtsu¹  Genki Kimura¹  Atsuyuki Okuda¹ 

[1] Department of Virology, Medical Institute of Bioregulation, Kyushu University 69

关键词: D123 protein;    proteasome;    protein degradation;    temperature-sensitive mutation;    reversion;   

DOI  :  10.1247/csf.26.205

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(21)Cited-By(1)A temperature-sensitive cell-cycle mutant of the 3Y1 rat fibroblast cell line, 3Y1tsD123 has in the D123 gene coding region a point mutation which causes instability of the D123 protein. Temperature-sensitive G1 arrest of the mutant is caused by increased degradation of the D123 protein at restrictive temperature. In this study we found that the selective proteasome inhibitors lactacystin and MG132 inhibited degradation of the mutated D123 protein in cell lines overexpressing the mutated D123 protein, followed by accumulation of a modified form (increased molecular weight other than by ubiquitination) of the D123 protein. Although a temperature-resistant revertant of the mutant had no further mutation in the D123 gene coding region, the modification of the mutated D123 protein was inhibited and the mutated D123 protein was rendered stable. The modification was also inhibited in the hybrid cell lines between the revertant and the cell line overexpressing the mutated D123 protein. These facts imply that the mutated D123 protein receives unidentified modification before degradation in the proteasome, and that the revertant expresses a gene inhibiting this modification.

【 授权许可】

Unknown