論文 - 詳細
| RRC ID | 77338 |
|---|---|
| 著者 | Ren R, Horton JR, Chen Q, Yang J, Liu B, Huang Y, Blumenthal RM, Zhang X, Cheng X. |
| タイトル | Structural basis for transcription factor ZBTB7A recognition of DNA and effects of ZBTB7A somatic mutations that occur in human acute myeloid leukemia. |
| ジャーナル | J Biol Chem |
| Abstract |
ZBTB7A belongs to a small family of transcription factors having three members in humans (7A, 7B, and 7C). They share a BTB/POZ protein interaction domain at the amino end and a zinc-finger DNA-binding domain at the carboxyl end. They control the transcription of a wide range of genes, having varied functions in hematopoiesis, oncogenesis, and metabolism (in particular glycolysis). ZBTB7A-binding profiles at gene promoters contain a consensus G(a/c)CCC motif, followed by a CCCC sequence in some instances. Structural and mutational investigations suggest that DNA-specific contacts with the four-finger tandem array of ZBTB7A are formed sequentially, initiated from ZF1-ZF2 binding to G(a/c)CCC before spreading to ZF3-ZF4, which bind the DNA backbone and the 3' CCCC sequence, respectively. Here, we studied some mutations found in t(8;21)-positive acute myeloid leukemia patients that occur within the ZBTB7A DNA-binding domain. We determined that these mutations generally impair ZBTB7A DNA binding, with the most severe disruptions resulting from mutations in ZF1 and ZF2, and the least from a frameshift mutation in ZF3 that results in partial mislocalization. Information provided here on ZBTB7A-DNA interactions is likely applicable to ZBTB7B/C, which have overlapping functions with ZBTB7A in controlling primary metabolism. |
| 巻・号 | 299(2) |
| ページ | 102885 |
| 公開日 | 2023-2-1 |
| DOI | 10.1016/j.jbc.2023.102885 |
| PII | S0021-9258(23)00017-0 |
| PMID | 36626981 |
| PMC | PMC9932118 |
| MeSH | Cell Line, Tumor DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Humans Leukemia, Myeloid, Acute* / genetics Mutation Protein Binding / genetics Protein Domains / genetics Transcription Factors* / genetics Transcription Factors* / metabolism Zinc Fingers / genetics |
| IF | 4.238 |
| 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 | 2 |
| 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 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |