論文 - 詳細
| RRC ID | 65405 |
|---|---|
| 著者 | Inukai R, Mori K, Kuwata K, Suzuki C, Maki M, Takahara T, Shibata H. |
| タイトル | The Novel ALG-2 Target Protein CDIP1 Promotes Cell Death by Interacting with ESCRT-I and VAPA/B. |
| ジャーナル | Int J Mol Sci |
| Abstract |
Apoptosis-linked gene 2 (ALG-2, also known as PDCD6) is a member of the penta-EF-hand (PEF) family of Ca2+-binding proteins. The murine gene encoding ALG-2 was originally reported to be an essential gene for apoptosis. However, the role of ALG-2 in cell death pathways has remained elusive. In the present study, we found that cell death-inducing p53 target protein 1 (CDIP1), a pro-apoptotic protein, interacts with ALG-2 in a Ca2+-dependent manner. Co-immunoprecipitation analysis of GFP-fused CDIP1 (GFP-CDIP1) revealed that GFP-CDIP1 associates with tumor susceptibility gene 101 (TSG101), a known target of ALG-2 and a subunit of endosomal sorting complex required for transport-I (ESCRT-I). ESCRT-I is a heterotetrameric complex composed of TSG101, VPS28, VPS37 and MVB12/UBAP1. Of diverse ESCRT-I species originating from four VPS37 isoforms (A, B, C, and D), CDIP1 preferentially associates with ESCRT-I containing VPS37B or VPS37C in part through the adaptor function of ALG-2. Overexpression of GFP-CDIP1 in HEK293 cells caused caspase-3/7-mediated cell death. In addition, the cell death was enhanced by co-expression of ALG-2 and ESCRT-I, indicating that ALG-2 likely promotes CDIP1-induced cell death by promoting the association between CDIP1 and ESCRT-I. We also found that CDIP1 binds to vesicle-associated membrane protein-associated protein (VAP)A and VAPB through the two phenylalanines in an acidic tract (FFAT)-like motif in the C-terminal region of CDIP1, mutations of which resulted in reduction of CDIP1-induced cell death. Therefore, our findings suggest that different expression levels of ALG-2, ESCRT-I subunits, VAPA and VAPB may have an impact on sensitivity of anticancer drugs associated with CDIP1 expression. |
| 巻・号 | 22(3) |
| 公開日 | 2021-1-25 |
| DOI | 10.3390/ijms22031175 |
| PII | ijms22031175 |
| PMID | 33503978 |
| PMC | PMC7865452 |
| MeSH | Amino Acid Motifs Amino Acid Sequence Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism* Binding Sites Calcium / metabolism Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism* Cell Death / genetics Cell Line Endosomal Sorting Complexes Required for Transport / metabolism* Humans Protein Binding Structure-Activity Relationship Vesicular Transport Proteins / metabolism* |
| IF | 4.556 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | Genome Network Project Human cDNA Clone IRAL009L17 (HGY083881) IRAL008O12 (HGY083548) |