PIAS1 interacts with the KRAB zinc finger protein, ZNF133, via zinc finger motifs and regulates its transcriptional activity

Lee, Sang-Jin; Lee, Jae-Rin; Hahn, Hwa-Sun; Kim, Young-Hoon; Ahn, Jin-Hyun; Bae, Chong Woo; Yang, Jun‐Mo; Hahn, Myong‐Joon

doi:10.1038/emm.2007.49

Cited by 17 publications

(14 citation statements)

References 32 publications

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“…However, it remains unknown which PRDM9 domain is responsible for this observed multimerization behavior. We sought to determine whether multimerization might involve PRDM9’s ZF domain in any way, given other examples of ZF domains mediating protein-protein interactions ( McCarty et al, 2003 ; Lee et al, 2007 ). To do so, we co-expressed PRDM9 constructs with different ZF domain properties and performed co-ImmunoPrecipitation (co-IP) experiments, thus extending our study from PRDM9’s DNA-binding properties to its protein binding properties.…”

Section: Resultsmentioning

confidence: 99%

A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis

Altemose

Noor

Bitoun

et al. 2017

eLife

143

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PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers.

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Section: Resultsmentioning

confidence: 99%

A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis

Altemose

Noor

Bitoun

et al. 2017

eLife

143

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“…Although LOC100043552 is classified as a pseudogene based on the presence of multiple termination codons, it exhibits 81% DNA homology to its human ortholog, ZNF133 , with conservation of the zinc finger motifs but not the KRAB domain. The in vivo function of ZNF133 is unknown, but it has been shown to function as a transcriptional repressor in vitro [31].…”

Section: Discussionmentioning

confidence: 99%

The PPCD1 Mouse: Characterization of a Mouse Model for Posterior Polymorphous Corneal Dystrophy and Identification of a Candidate Gene

et al. 2010

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The PPCD1 mouse, a spontaneous mutant that arose in our mouse colony, is characterized by an enlarged anterior chamber resulting from metaplasia of the corneal endothelium and blockage of the iridocorneal angle by epithelialized corneal endothelial cells. The presence of stratified multilayered corneal endothelial cells with abnormal patterns of cytokeratin expression are remarkably similar to those observed in human posterior polymorphous corneal dystrophy (PPCD) and the sporadic condition, iridocorneal endothelial syndrome. Affected eyes exhibit epithelialized corneal endothelial cells, with inappropriate cytokeratin expression and proliferation over the iridocorneal angle and posterior cornea. We have termed this the “mouse PPCD1” phenotype and mapped the mouse locus for this phenotype, designated “Ppcd1”, to a 6.1 Mbp interval on Chromosome 2, which is syntenic to the human Chromosome 20 PPCD1 interval. Inheritance of the mouse PPCD1 phenotype is autosomal dominant, with complete penetrance on the sensitive DBA/2J background and decreased penetrance on the C57BL/6J background. Comparative genome hybridization has identified a hemizygous 78 Kbp duplication in the mapped interval. The endpoints of the duplication are located in positions that disrupt the genes Csrp2bp and 6330439K17Rik and lead to duplication of the pseudogene LOC100043552. Quantitative reverse transcriptase-PCR indicates that expression levels of Csrp2bp and 6330439K17Rik are decreased in eyes of PPCD1 mice. Based on the observations of decreased gene expression levels, association with ZEB1-related pathways, and the report of corneal opacities in Csrp2bptm1a(KOMP)Wtsi heterozygotes and embryonic lethality in nulls, we postulate that duplication of the 78 Kbp segment leading to haploinsufficiency of Csrp2bp is responsible for the mouse PPCD1 phenotype. Similarly, CSRP2BP haploinsufficiency may lead to human PPCD.

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“…PIAS, specifically PIAS3, can bind the dimeric activated STAT3 and block the DNA-binding ability of STAT3 (Chung et al, 1997). In addition to preventing binding of activated STAT3 to the promoter region of its regulatory genes, PIAS can utilize its SUMO ligase activity to recruit co-repressors at the STAT3 transcriptional complex and thus modulate STAT3-mediated transcription (Yamashina et al, 2006; Lee et al, 2007). …”

Section: Regulation Of the Stat3 Activation Pathwaymentioning

confidence: 99%

Role of STAT3 in Transformation and Drug Resistance in CML

Nair¹,

Tolentino²,

Hazlehurst³

2012

Front. Oncol.

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Chronic myeloid leukemia (CML) is initially driven by the bcr–abl fusion oncoprotein. The identification of bcr–abl led to the discovery and rapid translation into the clinic of bcr–abl kinase inhibitors. Although, bcr–abl inhibitors are efficacious, experimental evidence indicates that targeting bcr–abl is not sufficient for elimination of minimal residual disease found within the bone marrow (BM). Experimental evidence indicates that the failure to eliminate the leukemic stem cell contributes to persistent minimal residual disease. Thus curative strategies will likely need to focus on strategies where bcr–abl inhibitors are given in combination with agents that specifically target the leukemic stem cell or the leukemic stem cell niche. One potential target to be exploited is the Janus kinase (JAK)/signal transducers and activators of transcription 3 (STAT3) pathway. Recently using STAT3 conditional knock-out mice it was shown that STAT3 is critical for initiating the disease. Interestingly, in the absence of treatment, STAT3 was not shown to be required for maintenance of the disease, suggesting that STAT3 is required only in the tumor initiating stem cell population (Hoelbl et al., 2010). In the context of the BM microenvironment, STAT3 is activated in a bcr–abl independent manner by the cytokine milieu. Activation of JAK/STAT3 was shown to contribute to cell survival even in the event of complete inhibition of bcr–abl activity within the BM compartment. Taken together, these studies suggest that JAK/STAT3 is an attractive therapeutic target for developing strategies for targeting the JAK–STAT3 pathway in combination with bcr–abl kinase inhibitors and may represent a viable strategy for eliminating or reducing minimal residual disease located in the BM in CML.

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PIAS1 interacts with the KRAB zinc finger protein, ZNF133, via zinc finger motifs and regulates its transcriptional activity

Cited by 17 publications

References 32 publications

A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis

A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis

The PPCD1 Mouse: Characterization of a Mouse Model for Posterior Polymorphous Corneal Dystrophy and Identification of a Candidate Gene

Role of STAT3 in Transformation and Drug Resistance in CML

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