The Conserved 12-Amino Acid Stretch in the Inter-Bromodomain Region of BET Family Proteins Functions as a Nuclear Localization Signal
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- Fukazawa Hidesuke
- Department of Bioactive Molecules, National Institute of Infectious Diseases Department of Bioactive Molecules, National Institute of Infectious Diseases
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- Masumi Atsuko
- Department of Blood and Biological Products, National Institute of Infectious Diseases Department of Blood and Biological Products, National Institute of Infectious Diseases
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The bromodomain and extraterminal (BET) family is a group of chromatin-binding proteins characterized by two bromodomains, an extraterminal (ET) domain, and several other conserved regions of unknown function. In humans, the BET family consists of four members, BRD2, BRD3, BRD4 and BRDT, that all normally localize to the nucleus. We identified a 12-amino acid stretch in the inter-bromodomain region that is perfectly conserved among the BET family members. We deleted these residues and expressed the mutant proteins in HEK293T cells to investigate the function of this motif. We found that the deletion of this motif alters the localization of BET proteins. Mutated BRD3 and BRD4 were excluded from the nucleus, and BRDT was found to be diffused throughout the nucleus and cytoplasm. Although the mutant BRD2 remained predominantly in the nucleus, a punctate distribution was also observed in the cytosol. It has been reported that a conserved motif between the second bromodomain and the ET domain serves as a nuclear localization signal for BRD2. Nevertheless, BET mutants lacking the reported nuclear localization signal motif but retaining the 12-amino acid stretch resided in the nucleus. Furthermore, these mutants were diffused throughout the cytoplasm when the 12 residues were removed. These results indicate that the conserved amino acid stretch in the inter-bromodomain region of the BET family functions as a nuclear localization signal.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 35 (11), 2064-2068, 2012
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679609424384
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- NII論文ID
- 130001872264
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC38bmtlGksg%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 024033124
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- PubMed
- 22971749
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可