期刊
ZOOLOGICAL SCIENCE
卷 31, 期 11, 页码 735-740出版社
ZOOLOGICAL SOC JAPAN
DOI: 10.2108/zs140049
关键词
Mlr; nucleolar protein 4; C-terminal binding protein; transcription coregulator; neurite pruning
类别
资金
- Grants-in-Aid for Scientific Research [26850218, 26291068] Funding Source: KAKEN
Mlr1 (Mblk-1-related protein-1) and Mlr2 are mouse homologs of transcription factor Mblk-1 (Mushroom body large-type Kenyon cell-specific protein-1), which we originally identified from the honeybee brain. In the present study, aiming at identifying coregulator(s) of Mlr1 and Mlr2 from the mouse brain, we used yeast two-hybrid screening of mouse brain cDNA library to search for interaction partners of Mlr 1 and Mlr2, respectively. We identified nucleolar protein 4 (NOL4) splicing variants as major interaction partners for both Mlr1 and Mlr2. Among the three murine NOL4 splicing variants, we further characterized NOL4-S, which lacks an N-terminal part of NOL4-L, and NOL4-S Delta, which lacks nuclear localization signal (NLS)-containing domain of NOL4-S. A GST pull-down assay revealed that Mlr1 interacts with both NOL4-S and NOL4-S Delta, whereas Mlr2 interacts with NOL4-S, but not with NOL4-S Delta. These results indicate that the NLS-containing domain of NO4-S is necessary for in vitro binding with Mlr2, but not for that with Mlr1. Furthermore, a luciferase assay using Schneider's Line 2 cells revealed that transactivation activity of Mlr1 was significantly suppressed by both NOL4-S and NOL4-S Delta, with almost complete suppression by NOL4-S Delta. In contrast, transactivation activity of Mlr2 was significantly suppressed by NOL4-S but rather activated by NOL4-S Delta. Our findings suggest that transactivation activities of Mlr1 and Mlr2 are differentially regulated by splicing variants of NOL4, which are expressed in a tissue-selective manner.
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