Role of zinc finger structure in nuclear localization of transcription factor Sp1

Itö, Tatsuo; Azumano, Makiko; Uwatoko, Chisana; Itoh, Kohji; Kuwahara, Jun

doi:10.1016/j.bbrc.2008.12.165

Cited by 31 publications

(19 citation statements)

References 27 publications

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“…We have previously observed that the KRAB domain is able to reinforce nuclear localization activity of KRAB-ZFPs by interacting with KAP1 [25]. Meanwhile, nuclear localization signal (NLS) of several zinc finger proteins have been identified that localize in the zinc fingers [26]–[29], consistent with the finding that NLS overlaps the DNA or RNA binding domains of nucleic acid-binding proteins [30].…”

Section: Introductionsupporting

confidence: 67%

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

et al. 2014

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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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Section: Introductionsupporting

confidence: 67%

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

et al. 2014

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“…[65]–[67]). Indeed, some C2H2 ZNF proteins have been shown to contain non-classical nuclear localization sequences in their zinc finger domains [68]–[70]. Thus, it is likely that different KRAB-ZNF proteins will have different properties and behavior with respect to their spatial distribution and dynamics.…”

Section: Discussionmentioning

confidence: 99%

The B-Subdomain of the Xenopus laevis XFIN KRAB-AB Domain Is Responsible for Its Weaker Transcriptional Repressor Activity Compared to Human ZNF10/Kox1

2014

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The Krüppel-associated box (KRAB) domain interacts with the nuclear hub protein TRIM28 to initiate or mediate chromatin-dependent processes like transcriptional repression, imprinting or suppression of endogenous retroviruses. The prototype KRAB domain initially identified in ZNF10/KOX1 encompasses two subdomains A and B that are found in hundreds of zinc finger transcription factors studied in human and murine genomes. Here we demonstrate for the first time transcriptional repressor activity of an amphibian KRAB domain. After sequence correction, the updated KRAB-AB domain of zinc finger protein XFIN from the frog Xenopus laevis was found to confer transcriptional repression in reporter assays in Xenopus laevis A6 kidney cells as well as in human HeLa, but not in the minnow Pimephales promelas fish cell line EPC. Binding of the XFIN KRAB-AB domain to human TRIM28 was demonstrated in a classical co-immunoprecipitation approach and visualized in a single-cell compartmentalization assay. XFIN-AB displayed reduced potency in repression as well as lower strength of interaction with TRIM28 compared to ZNF10 KRAB-AB. KRAB-B subdomain swapping between the two KRAB domains indicated that it was mainly the KRAB-B subdomain of XFIN that was responsible for its lower capacity in repression and binding to human TRIM28. In EPC fish cells, ZNF10 and XFIN KRAB repressor activity could be partially restored to low levels by adding exogenous human TRIM28. In contrast to XFIN, we did not find any transcriptional repression activity for the KRAB-like domain of human PRDM9 in HeLa cells. PRDM9 is thought to harbor an evolutionary older domain related to KRAB whose homologs even occur in invertebrates. Our results support the notion that functional bona fide KRAB domains which confer transcriptional repression and interact with TRIM28 most likely co-evolved together with TRIM28 at the beginning of tetrapode evolution.

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“…It has been reported that tertiary structure of C 2 H 2 -type zinc finger motifs is necessary for nuclear localization of NGFI-A and Sp1 [15], [33]. Moreover, basic amino acids within C 2 H 2 -type zinc finger motifs are essential for nuclear localization of EKLF/KLF1 and ZIC3 [27], [31].…”

Section: Discussionmentioning

confidence: 99%

The LSD1-Type Zinc Finger Motifs of Pisum sativa LSD1 Are a Novel Nuclear Localization Signal and Interact with Importin Alpha

Huang

Zhang

et al. 2011

PLoS ONE

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BackgroundGenetic studies of the Arabidopsis mutant lsd1 highlight the important role of LSD1 in the negative regulation of plant programmed cell death (PCD). Arabidopsis thaliana LSD1 (AtLSD1) contains three LSD1-type zinc finger motifs, which are involved in the protein–protein interaction.Methodology/Principal FindingsTo further understand the function of LSD1, we have analyzed cellular localization and functional localization domains of Pisum sativa LSD1 (PsLSD1), which is a homolog of AtLSD1. Subcellular localization analysis of green fluorescent protein (GFP)-tagged PsLSD1 indicates that PsLSD1 is localized in the nucleus. Using a series of GFP-tagged PsLSD1 deletion mutants, we found that the three LSD1-type zinc finger motifs of PsLSD1 alone can target GFP to the nucleus, whereas deletion of the three zinc finger motifs or any individual zinc finger motif causes PsLSD1 to lose its nuclear localization, indicating that the three zinc finger motifs are necessary and sufficient for its nuclear localization. Moreover, site-directed mutagenesis analysis of GFP-tagged PsLSD1 indicates that tertiary structure and basic amino acids of each zinc finger motif are necessary for PsLSD1 nuclear localization. In addition, yeast two-hybrid, pull-down, and BiFC assays demonstrate that the three zinc finger motifs of PsLSD1 directly bind to importin α in vitro and in vivo.Conclusions/SignificanceOur data demonstrate that the LSD1-type zinc finger motifs of PsLSD1 are a novel nuclear localization signal and directly bind to importin α, and suggest that the nuclear import of LSD1 may rely on the interaction between its zinc finger motifs and importin α. Moreover, the nuclear localization of PsLSD1 suggests that LSD1 may function as a transcription regulator involved in negatively regulating PCD.

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Role of zinc finger structure in nuclear localization of transcription factor Sp1

Cited by 31 publications

References 27 publications

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

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

The B-Subdomain of the Xenopus laevis XFIN KRAB-AB Domain Is Responsible for Its Weaker Transcriptional Repressor Activity Compared to Human ZNF10/Kox1

The LSD1-Type Zinc Finger Motifs of Pisum sativa LSD1 Are a Novel Nuclear Localization Signal and Interact with Importin Alpha

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