Zinc fingers are known as domains for binding DNA and RNA. Do they also mediate protein-protein interactions?

Loughlin, Fionna E.; Mackay, Joel P.

doi:10.1080/15216540600868445

Cited by 5 publications

(5 citation statements)

References 27 publications

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“…C2H2 ZnF proteins likely constitute the largest family of regulatory proteins in mammals ( 59 , 66 – 68 ). They can interact with DNA, RNA and proteins, and modulate an array of biological processes, such as development, differentiation and tumor suppression ( 69 , 70 ). The ZnF enables Gis1 to bind to DNA, and is essential for transcriptional activation by Gis1.…”

Section: Discussionmentioning

confidence: 99%

Heme promotes transcriptional and demethylase activities of Gis1, a member of the histone demethylase JMJD2/KDM4 family

Lal

Comer

Konduri

et al. 2017

Nucleic Acids Research

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The yeast Gis1 protein is a transcriptional regulator belonging to the JMJD2/KDM4 subfamily of demethylases that contain a JmjC domain, which are highly conserved from yeast to humans. They have important functions in histone methylation, cellular signaling and tumorigenesis. Besides serving as a cofactor in many proteins, heme is known to directly regulate the activities of proteins ranging from transcriptional regulators to potassium channels. Here, we report a novel mechanism governing heme regulation of Gis1 transcriptional and histone demethylase activities. We found that two Gis1 modules, the JmjN + JmjC domain and the zinc finger (ZnF), can bind to heme specifically in vitro. In vivo functional analysis showed that the ZnF, not the JmjN + JmjC domain, promotes heme activation of transcriptional activity. Likewise, measurements of the demethylase activity of purified Gis1 proteins showed that full-length Gis1 and the JmjN + JmjC domain both possess demethylase activity. However, heme potentiates the demethylase activity of full-length Gis1, but not that of the JmjN + JmjC domain, which can confer heme activation of transcriptional activity in an unrelated protein. These results demonstrate that Gis1 represents a novel class of multi-functional heme sensing and signaling proteins, and that heme binding to the ZnF stimulates Gis1 demethylase and transcriptional activities.

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Section: Discussionmentioning

confidence: 99%

Heme promotes transcriptional and demethylase activities of Gis1, a member of the histone demethylase JMJD2/KDM4 family

Lal

Comer

Konduri

et al. 2017

Nucleic Acids Research

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“…The ZF domain comprises two pairs of conserved cysteine and/or histidine residues, which coordinate with a lone zinc ion to configure a finger-like loop structure, thus enhancing the stability of the motif [7]. Zinc finger domain is related to protein nucleic acid recognition and protein-protein interaction [8,9]. Based on conserved motifs and phylogenetic relationships, ZF-HD gene family is essentially classified to two subfamilies: ZHD and MIF (mini zinc finger) subfamilies [10].…”

Section: Introductionmentioning

confidence: 99%

Systematic Analysis of Zinc Finger-Homeodomain Transcription Factors (ZF-HDs) in Barley (Hordeum vulgare L.)

Liu,

Liu

et al. 2024

Genes

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Zinc finger-homeodomain transcription factors (ZF-HDs) are pivotal in regulating plant growth, development, and diverse stress responses. In this study, we found 8 ZF-HD genes in barley genome. Theses eight HvZF-HD genes were located on five chromosomes, and classified into ZHD and MIF subfamily. The collinearity, gene structure, conserved motif, and cis-elements of HvZF-HD genes were also analyzed. Real-time PCR results suggested that the expression of HvZF-HD4, HvZF-HD6, HvZF-HD7 and HvZF-HD8 were up-regulated after hormones (ABA, GA3 and MeJA) or PEG treatments, especially HvZF-HD6 was significantly induced. These results provide useful information of ZF-HD genes to future study aimed at barley breeding.

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“…Zinc finger proteins are known to exert diverse activities through interaction with a variety of molecules (Laity et al 2001;Krishna et al 2003;Loughlin and Mackay 2006), but the activity for ZFP871 has not been explored. Since PCBP4 regulates both p53 and ZFP871 expression, we explored whether ZFP871 plays a role in the PCBP4-mediated regulation of p53 expression.…”

Section: Zfp871 Modulates Cell Growth By Targeting P53 For Degradationmentioning

confidence: 99%

“…Zinc finger proteins represent a group of protein families with an array of functions in transcription and protein degradation (Laity et al 2001;Krishna et al 2003;Loughlin and Mackay 2006). Interestingly, MDM2, MDMX, and Pirh2 are proteins containing a zinc finger domain (Yu et al 2006;Lee and Gu 2010;Shloush et al 2011).…”

Section: Zfp871 Targets P53 For Degradationmentioning

confidence: 99%

“…Thus, we postulate that ZFP871 is part of a ubiquitin E3 ligase, such as MDM2, that targets p53 for proteosomal degradation. Indeed, zinc finger proteins often serve as a scaffold for protein-protein interactions (Laity et al 2001;Loughlin and Mackay 2006;Tian et al 2009). We also found that ZFP871 physically interacts with MDM2 and p53, and thus ZFP871 may be a part of the MDM2 E3 ligase that targets p53 for degradation.…”

Section: Zfp871 Targets P53 For Degradationmentioning

confidence: 99%

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Mice deficient in poly(C)-binding protein 4 are susceptible to spontaneous tumors through increased expression of ZFP871 that targets p53 for degradation

et al. 2016

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Poly(C)-binding protein 4 (PCBP4), also called MCG10 and a target of p53, plays a role in the cell cycle and is implicated in lung tumor suppression. Here, we found that PCBP4-deficient mice are prone to lung adenocarcinoma, lymphoma, and kidney tumor and that PCBP4-deficient mouse embryo fibroblasts (MEFs) exhibit enhanced cell proliferation but decreased cellular senescence. We also found that p53 expression is markedly reduced in PCBP4-deficient MEFs and mouse tissues, suggesting that PCBP4 in turn regulates p53 expression. To determine how PCBP4 regulates p53 expression, PCBP4 targets were identified by RNA immunoprecipitation followed by RNA sequencing (RNA-seq). We found that the transcript encoding ZFP871 (zinc finger protein 871; also called ZNF709 in humans) interacts with and is regulated by PCBP4 via mRNA stability. Additionally, we found that ZFP871 physically interacts with p53 and MDM2 proteins. Consistently, ectopic expression of ZFP871 decreases-whereas knockdown of ZFP871 increases-p53 protein stability through a proteasome-dependent degradation pathway. Moreover, loss of ZFP871 reverses the reduction of p53 expression by lack of PCBP4, and thus increased expression of ZFP871 is responsible for decreased expression of p53 in the PCBP4-deficient MEFs and mouse tissues. Interestingly, we found that, like PCBP4, ZFP871 is also regulated by DNA damage and p53. Finally, we showed that knockdown of ZFP871 markedly enhances p53 expression, leading to growth suppression and apoptosis in a p53-dependent manner. Thus, the p53-PCBP4-ZFP871 axis represents a novel feedback loop in the p53 pathway. Together, we hypothesize that PCBP4 is a potential tissue-specific tumor suppressor and that ZFP871 is part of MDM2 and possibly other ubiquitin E3 ligases that target p53 for degradation.

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Zinc fingers are known as domains for binding DNA and RNA. Do they also mediate protein-protein interactions?

Cited by 5 publications

References 27 publications

Heme promotes transcriptional and demethylase activities of Gis1, a member of the histone demethylase JMJD2/KDM4 family

Heme promotes transcriptional and demethylase activities of Gis1, a member of the histone demethylase JMJD2/KDM4 family

Systematic Analysis of Zinc Finger-Homeodomain Transcription Factors (ZF-HDs) in Barley (Hordeum vulgare L.)

Mice deficient in poly(C)-binding protein 4 are susceptible to spontaneous tumors through increased expression of ZFP871 that targets p53 for degradation

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