Zinc fingers function cooperatively with KRAB domain for nuclear localization of KRAB-containing zinc finger proteins

Multiple nuclear localization domains have been identified in nuclear proteins, and they finely control nuclear import and functions of those proteins. ZNF268 is a typical KRAB-containing zinc finger protein (KRAB-ZFP), and previous studies have shown that the KRAB domain reinforces nuclear localiza...

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Bibliographic Details
Published in:PloS one 2014-03, Vol.9 (3), p.e92155
Main Authors: Wang, Wei, Cai, Jinyang, Lin, Yi, Liu, Zikou, Ren, Qihao, Hu, Li, Huang, Zan, Guo, Mingxiong, Li, Wenxin
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Cell Nucleolus - metabolism
Cell Nucleus - metabolism
Deoxyribonucleic acid
DNA
DNA binding proteins
Fingers
Gene expression
HeLa Cells
Humans
Karyopherins - metabolism
Laboratories
Life sciences
Localization
Mutagenesis
Mutant Proteins - metabolism
Mutation - genetics
Nuclear Localization Signals
Nuclear Proteins - chemistry
Nuclear Proteins - metabolism
Nuclear transport
Nucleoli
Protein Binding
Protein Structure, Tertiary
Protein Transport
Proteins
Rodents
Structure-Activity Relationship
Transcription factors
Virology
Zinc
Zinc finger proteins
Zinc Fingers
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Summary:Multiple nuclear localization domains have been identified in nuclear proteins, and they finely control nuclear import and functions of those proteins. ZNF268 is a typical KRAB-containing zinc finger protein (KRAB-ZFP), and previous studies have shown that the KRAB domain reinforces nuclear localization of KRAB-ZFPs by interacting with KAP1. In this study, we find that some of 24 zinc fingers of ZNF268 also possess nuclear localization activity. Results of mutagenesis studies suggest that KRAB and zinc fingers are both necessary, and they function both independently and cooperatively for the nuclear localization of ZNF268. However, the subnuclear targeting activities of KRAB and zinc fingers are different. KRAB targets proteins in nucleoplasm, but not in the nucleolus, which is mediated by interaction with KAP1, while zinc fingers target proteins in the whole nucleus uniformly. The cooperative activities of KAP1-KRAB-zinc fingers result in the precise nucleoplasmic, but not nucleolar localization of KRAB-ZFPs. Our studies reveal a novel mechanism for the subcellular localization of KRAB-ZFPs and may help us to further explore their biological functions.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0092155