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Zinc Fingers Function Cooperatively with KRAB Domain for Nuclear Localization of KRAB-containing Zinc Finger Proteins

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Journal PLoS One
Date 2014 Mar 21
PMID 24647005
Citations 9
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Abstract

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.

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References
1.
Ito T, Azumano M, Uwatoko C, Itoh K, Kuwahara J . Role of zinc finger structure in nuclear localization of transcription factor Sp1. Biochem Biophys Res Commun. 2009; 380(1):28-32. DOI: 10.1016/j.bbrc.2008.12.165. View

2.
Bellefroid E, Poncelet D, Lecocq P, Revelant O, Martial J . The evolutionarily conserved Krüppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc Natl Acad Sci U S A. 1991; 88(9):3608-12. PMC: 51501. DOI: 10.1073/pnas.88.9.3608. View

3.
Savory J, Hsu B, Laquian I, GIFFIN W, Reich T, Hache R . Discrimination between NL1- and NL2-mediated nuclear localization of the glucocorticoid receptor. Mol Cell Biol. 1999; 19(2):1025-37. PMC: 116033. DOI: 10.1128/MCB.19.2.1025. View

4.
Guo M, Wang D, Shao H, Qiu H, Xue L, Zhao Z . Transcription of human zinc finger ZNF268 gene requires an intragenic promoter element. J Biol Chem. 2006; 281(34):24623-36. DOI: 10.1074/jbc.M602753200. View

5.
Do H, Song H, Yang H, Kim D, Kim N, Kim J . Identification of multiple nuclear localization signals in murine Elf3, an ETS transcription factor. FEBS Lett. 2006; 580(7):1865-71. DOI: 10.1016/j.febslet.2006.02.049. View