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Molecular Mechanisms of Zinc Finger Proteins in Biological Processes and Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (20 June 2025) | Viewed by 3945

Special Issue Editors

Dr. Amelia Casamassimi

E-Mail
Guest Editor
Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
Interests: cancer; PRDM genes; transcriptional regulation
Special Issues, Collections and Topics in MDPI journals
Dr. Patrizia Gazzerro

E-Mail Website
Guest Editor
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Salerno, Italy
Interests: cancer; targeted therapy; metabolic pathway; PRDM genes

Special Issue Information

Dear Colleagues,

Zinc finger proteins (ZFPs) are ubiquitous in biology, playing a pivotal role in mediating interactions with DNA, RNA, and other proteins. These proteins are crucial for transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, DNA repair, cell migration, and a broad array of other biological processes.

ZFPs exhibit diverse zinc finger motifs for specific interactions. Cys2His2, the most abundant type, is found in 700+ human proteins, serving as transcription factors. CTCF, a chromatin regulator, has 11 conserved zinc fingers for gene expression control.

ZFPs combine with other domains, enhancing complexity and functions. These domains include Krüppel-associated box (KRAB), SCAN, the zinc finger-associated domain (ZAD), etc. PRDM (Positive Regulatory Domain) proteins, with a PR domain and zinc fingers, modulate gene expression by chromatin modification, involved in proliferation, differentiation, cell cycle, stemness, and immune cell homeostasis. Remarkably, given this wide range of functions, their disruption may contribute to the onset and progression of several human diseases. Similarly, other ZFPs, such as GATA family proteins, nuclear receptors, etc., have been established to play a pathophysiological role in humans.

We invite authors to submit research and reviews on ZFP transcriptional regulation in development, cell homeostasis, and diseases, providing insights across biological systems.

Dr. Amelia Casamassimi
Dr. Patrizia Gazzerro
Guest Editors

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Keywords

  • zinc finger domain
  • CTCF
  • PRDM family
  • nuclear receptors
  • human diseases
  • transcriptional regulation
  • epigenetic modifications

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Published Papers (4 papers)

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Research

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14 pages, 1847 KiB  
Communication
The Plasmodium falciparum RING Finger Protein PfRNF1 Forms an Interaction Network with Regulators of Sexual Development
by Afia Farrukh, Sherihan Musa, Ute Distler, Stefan Tenzer, Gabriele Pradel and Che Julius Ngwa
Int. J. Mol. Sci. 2025, 26(12), 5470; https://doi.org/10.3390/ijms26125470 - 7 Jun 2025
Viewed by 321
Abstract
RNA-binding E3 ubiquitin ligases (RBULs) provide a link between RNA metabolic processes and the ubiquitin proteasome system (UPS). In humans, RBULs are involved in various biological processes, such as cell proliferation and differentiation, as well as sexual development. To date, little is known [...] Read more.
RNA-binding E3 ubiquitin ligases (RBULs) provide a link between RNA metabolic processes and the ubiquitin proteasome system (UPS). In humans, RBULs are involved in various biological processes, such as cell proliferation and differentiation, as well as sexual development. To date, little is known about their role in the protozoan parasite Plasmodium falciparum, the causative agent of malaria tropica. We previously identified a novel P. falciparum RBUL, the RING finger E3 ligase PfRNF1, which is highly expressed during gametocyte development. Here, we conducted BioID-based proximity interaction studies to unveil the PfRNF1 interactome. We show that in immature gametocytes, PfRNF1 forms an interaction network that is mainly composed of RNA-binding proteins, including the translational repressors DOZI and CITH and members of the CCR4-NOT complex, as well as UPS-related proteins. In particular, PfRNF1 interacts with recently identified regulators of sexual development like the zinc finger protein PfMD3, with which it shares the majority of interactors. The common interactome of PfRNF1 and PfMD3 comprises several uncharacterized proteins predominantly expressed in male or female gametocytes. Our results demonstrate that PfRNF1 engages with RNA-binding proteins crucial for sex determination in gametocytes, thereby linking posttranscriptional regulation with the UPS. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Zinc Finger Proteins in Biological Processes and Diseases)
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12 pages, 1865 KiB  
Article
A Possible Phenotype-to-Genotype Association of Novel Single-Nucleotide Variants in the Coding Exons of the ZNF469 Gene to Arterial Aneurysmal and Dissection Diseases
by Adam Wolf, Peyton Moore, Charles Hong and Mohanakrishnan Sathyamoorthy
Int. J. Mol. Sci. 2024, 25(24), 13730; https://doi.org/10.3390/ijms252413730 - 23 Dec 2024
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Abstract
After reporting the first known clinical case associating compound heterozygous single-nucleotide variants in Exon 2 of ZNF469 to aortic aneurysmal and iliac dissection, we began prospective surveillance in our vascular genetic practice for similar cases. Herein, we present nine (9) subjects from a [...] Read more.
After reporting the first known clinical case associating compound heterozygous single-nucleotide variants in Exon 2 of ZNF469 to aortic aneurysmal and iliac dissection, we began prospective surveillance in our vascular genetic practice for similar cases. Herein, we present nine (9) subjects from a total cohort of 135 with arterial aneurysms or dissections who revealed single-nucleotide variants in ZNF469 with no other alterations in a panel of 35 genes associated with aneurysmal and dissection disorders. Five out of nine (5/9) single-nucleotide variants were in Exon 1, and four out of nine (4/9) mutations were in Exon 2, both of which are principal coding exons for this gene. Eight out of nine (8/9) were ACMG variants of unknown significance (VUSs), and one out of nine (1/9) was an ACMG pathogenic mutation previously associated to brittle cornea syndrome (BCS). Of our nine subjects, four (44.4%) experienced clinically significant vascular dissection, and four (44.4%) had a family history of one or more first-degree relatives with aneurysmal or dissection diseases. This novel genetic case series significantly strengthens our initial discovery of ZNF469’s potential association with arterial aneurysmal/dissection diseases through the study of this cohort of unrelated patients. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Zinc Finger Proteins in Biological Processes and Diseases)
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16 pages, 28417 KiB  
Article
Transcriptomic Identification of Potential C2H2 Zinc Finger Protein Transcription Factors in Pinus massoniana in Response to Biotic and Abiotic Stresses
by Dengbao Wang, Zimo Qiu, Tao Xu, Sheng Yao, Meijing Chen, Qianzi Li, Romaric Hippolyte Agassin and Kongshu Ji
Int. J. Mol. Sci. 2024, 25(15), 8361; https://doi.org/10.3390/ijms25158361 - 31 Jul 2024
Cited by 1 | Viewed by 1461
Abstract
Biotic and abiotic stresses have already seriously restricted the growth and development of Pinus massoniana, thereby influencing the quality and yield of its wood and turpentine. Recent studies have shown that C2H2 zinc finger protein transcription factors play an important role in [...] Read more.
Biotic and abiotic stresses have already seriously restricted the growth and development of Pinus massoniana, thereby influencing the quality and yield of its wood and turpentine. Recent studies have shown that C2H2 zinc finger protein transcription factors play an important role in biotic and abiotic stress response. However, the members and expression patterns of C2H2 TFs in response to stresses in P. massoniana have not been performed. In this paper, 57 C2H2 zinc finger proteins of P. massoniana were identified and divided into five subgroups according to a phylogenetic analysis. In addition, six Q-type PmC2H2-ZFPs containing the plant-specific motif ‘QALGGH’ were selected for further study under different stresses. The findings demonstrated that PmC2H2-ZFPs exhibit responsiveness towards various abiotic stresses, including drought, NaCl, ABA, PEG, H2O2, etc., as well as biotic stress caused by the pine wood nematode. In addition, PmC2H2-4 and PmC2H2-20 were nuclear localization proteins, and PmC2H2-20 was a transcriptional activator. PmC2H2-20 was selected as a potential transcriptional regulator in response to various stresses in P. massoniana. These findings laid a foundation for further study on the role of PmC2H2-ZFPs in stress tolerance. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Zinc Finger Proteins in Biological Processes and Diseases)
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Review

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23 pages, 2513 KiB  
Review
The Multifaceted Roles of Zinc Finger Proteins in Pluripotency and Reprogramming
by Yiwei Qian and Qiang Wu
Int. J. Mol. Sci. 2025, 26(11), 5106; https://doi.org/10.3390/ijms26115106 - 26 May 2025
Viewed by 456
Abstract
Zinc finger proteins (ZFPs) play a crucial role in regulating gene expression. In recent years, there has been increasing evidence highlighting the importance of zinc finger proteins in pluripotent stem cells, which hold great promise in regenerative medicine. The general mechanism by which [...] Read more.
Zinc finger proteins (ZFPs) play a crucial role in regulating gene expression. In recent years, there has been increasing evidence highlighting the importance of zinc finger proteins in pluripotent stem cells, which hold great promise in regenerative medicine. The general mechanism by which zinc finger proteins function in gene regulation of pluripotent stem cells involves their interaction with core transcriptional regulatory networks. ZFPs can either enhance key pluripotency genes to maintain pluripotency or promote differentiation of stem cells towards specific lineages by suppressing these key pluripotency genes. Hence, understanding the role of ZFPs in pluripotency and reprogramming is crucial for unraveling the complex regulatory network that governs cell fate decisions. Here we provide a comprehensive review of the current knowledge regarding the multifaceted role of ZFPs in pluripotency maintenance and reprogramming. We propose that more efforts should be focused on fully understanding the fascinating functions of ZFPs in stem cell fate decision. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Zinc Finger Proteins in Biological Processes and Diseases)
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