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Physiological and Pathological Functions of Zinc Finger Proteins
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Physiological and Pathological Functions of Zinc Finger Proteins

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

Deadline for manuscript submissions: 20 August 2024 | Viewed by 5446

Special Issue Editors

Dr. Paola Costanzo

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80138 Naples, Italy
Interests: transcriptional and epigenetic regulation; KRAB-Zinc finger proteins; haematological malignancies; melanoma; signalling pathways
Dr. Elena Cesaro

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, Italy
Interests: transcriptional regulation; epigenetic mechanisms of gene expression regulation; signal transduction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In this Special Issue, we aim to gain new insight into the wide range of cellular processes governed by zinc finger proteins (ZFPs) under normal physiological and pathological conditions. The zinc finger protein (ZFP) family is one of the largest families of proteins with DNA-binding activity in eukaryotic genomes. To date, different classes of zinc finger motifs have been described according to the nature and spacing of their zinc-chelating residues. These motifs, in addition to binding directly to DNA, can mediate RNA-binding and also protein–protein and protein–lipid interactions. Several ZFPs, in addition to containing multiple zinc finger motifs, often from different classes,  also contain additional protein domains, such as the BTB/POZ, SCAN, and KRAB domains, which, interacting with different molecular partners, contribute to the functional diversification of the ZFP family.

ZFPs have a crucial role both in cellular homeostasis and disease. Indeed, these proteins are involved in transcriptional regulation and the establishment and maintenance of chromatin structure through the recruitment of DNA methyltransferase or histone-modifying enzymes on gene targets. In addition, ZFPs participate in various other cellular processes, including signal transduction, ubiquitin-mediated protein degradation, DNA repair, and cell migration.

Accumulating evidence indicates that alterations in ZFPs are involved in the onset and progression of several diseases such as inflammatory disorders, neurodegeneration, and congenital heart disease. ZFPs are also closely related to cancer progression and metastasis formation, acting as a tumour suppressor and/or oncogene.

We warmly welcome contributions, including original papers and reviews, that shed novel light on the functions and mechanisms of action of ZFPs in health and disease.

Dr. Paola Costanzo
Dr. Elena Cesaro
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • zinc finger
  • transcriptional regulation
  • epigenetic
  • signal transduction
  • cellular homeostasis
  • human disease

Published Papers (4 papers)

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Research

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24 pages, 5256 KiB  
Article
ZNF643/ZFP69B Exerts Oncogenic Properties and Associates with Cell Adhesion and Immune Processes
by Urszula Oleksiewicz, Marta Machnik, Joanna Sobocińska, Sara Molenda, Anna Olechnowicz, Anna Florczak, Julia Mierzejewska, Dominika Adamczak, Mikołaj Smolibowski, Mariusz Kaczmarek and Andrzej Mackiewicz
Int. J. Mol. Sci. 2023, 24(22), 16380; https://doi.org/10.3390/ijms242216380 - 15 Nov 2023
Viewed by 1234
Abstract
The global cancer burden remains high; thus, a better understanding of the molecular mechanisms driving carcinogenesis is needed to improve current prevention and treatment options. We previously detected the ZNF643/ZFP69B gene upregulated in multiple tumors, and we speculated it may play a role [...] Read more.
The global cancer burden remains high; thus, a better understanding of the molecular mechanisms driving carcinogenesis is needed to improve current prevention and treatment options. We previously detected the ZNF643/ZFP69B gene upregulated in multiple tumors, and we speculated it may play a role in tumor biology. To test this hypothesis, we employed TCGA-centered databases to correlate ZNF643 status with various clinicopathological parameters. We also performed RNA-seq analysis and in vitro studies assessing cancer cell phenotypes, and we searched for ZNF643-bound genomic loci. Our data indicated higher levels of ZNF643 in most analyzed tumors compared to normal samples, possibly due to copy number variations. ZNF643 mRNA correlated with diverse molecular and immune subtypes and clinicopathological features (tumor stage, grade, patient survival). RNA-seq analysis revealed that ZNF643 silencing triggers the deregulation of the genes implicated in various cancer-related processes, such as growth, adhesion, and immune system. Moreover, we observed that ZNF643 positively influences cell cycle, migration, and invasion. Finally, our ChIP-seq analysis indicated that the genes associated with ZNF643 binding are linked to adhesion and immune signaling. In conclusion, our data confirm the oncogenic properties of ZNF643 and pinpoint its impact on cell adhesion and immune processes. Full article
(This article belongs to the Special Issue Physiological and Pathological Functions of Zinc Finger Proteins)
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12 pages, 18793 KiB  
Article
Zinc Finger 521 Modulates the Nrf2-Notch Signaling Pathway in Human Ovarian Carcinoma
by Stefania Scicchitano, Maria Concetta Faniello and Maria Mesuraca
Int. J. Mol. Sci. 2023, 24(19), 14755; https://doi.org/10.3390/ijms241914755 - 29 Sep 2023
Viewed by 880
Abstract
The human zinc finger protein 521 (ZNF521) is a co-transcriptional factor with multiple recognized regulatory functions in a range of normal, cancer and stem cell compartments. ZNF521 regulates proliferation, progression and CSC (cancer stem cell) compartments in human ovarian cancer (hOC), which is [...] Read more.
The human zinc finger protein 521 (ZNF521) is a co-transcriptional factor with multiple recognized regulatory functions in a range of normal, cancer and stem cell compartments. ZNF521 regulates proliferation, progression and CSC (cancer stem cell) compartments in human ovarian cancer (hOC), which is a very aggressive and late-diagnosed female tumor. Two other important regulators of hOC are the NRF2 and NOTCH signaling pathways. In the present paper, the mRNA and protein levels of ZNF521 were correlated with those of the NRF2-NOTCH signaling components in two different hOC cell lines and in a public dataset of 381 hOC patients. The data show that high levels of ZNF521 significantly increase NRF2-NOTCH signaling expression; conversely, the silencing of ZNF521 impairs NRF2-NOTCH signaling. This experimental work shows that, in hOC, different levels of ZNF521 modulate the NRF2-NOTCH signaling pathway and also influences hOC CSC properties. Full article
(This article belongs to the Special Issue Physiological and Pathological Functions of Zinc Finger Proteins)
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Review

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15 pages, 1583 KiB  
Review
Regulating Protein–RNA Interactions: Advances in Targeting the LIN28/Let-7 Pathway
by Greater Kayode Oyejobi, Xiaodan Yan, Piotr Sliz and Longfei Wang
Int. J. Mol. Sci. 2024, 25(7), 3585; https://doi.org/10.3390/ijms25073585 - 22 Mar 2024
Viewed by 772
Abstract
Originally discovered in C. elegans, LIN28 is an evolutionarily conserved zinc finger RNA-binding protein (RBP) that post-transcriptionally regulates genes involved in developmental timing, stem cell programming, and oncogenesis. LIN28 acts via two distinct mechanisms. It blocks the biogenesis of the lethal-7 (let-7) [...] Read more.
Originally discovered in C. elegans, LIN28 is an evolutionarily conserved zinc finger RNA-binding protein (RBP) that post-transcriptionally regulates genes involved in developmental timing, stem cell programming, and oncogenesis. LIN28 acts via two distinct mechanisms. It blocks the biogenesis of the lethal-7 (let-7) microRNA (miRNA) family, and also directly binds messenger RNA (mRNA) targets, such as IGF-2 mRNA, and alters downstream splicing and translation events. This review focuses on the molecular mechanism of LIN28 repression of let-7 and current strategies to overcome this blockade for the purpose of cancer therapy. We highlight the value of the LIN28/let-7 pathway as a drug target, as multiple oncogenic proteins that the pathway regulates are considered undruggable due to their inaccessible cellular location and lack of cavities for small molecule binding. Full article
(This article belongs to the Special Issue Physiological and Pathological Functions of Zinc Finger Proteins)
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26 pages, 1067 KiB  
Review
The Roles of Zinc Finger Proteins in Colorectal Cancer
by Aishwarya S. Iyer, Mohammed Rifat Shaik, Jean-Pierre Raufman and Guofeng Xie
Int. J. Mol. Sci. 2023, 24(12), 10249; https://doi.org/10.3390/ijms241210249 - 16 Jun 2023
Cited by 2 | Viewed by 1873
Abstract
Despite colorectal cancer remaining a leading worldwide cause of cancer-related death, there remains a paucity of effective treatments for advanced disease. The molecular mechanisms underlying the development of colorectal cancer include altered cell signaling and cell cycle regulation that may result from epigenetic [...] Read more.
Despite colorectal cancer remaining a leading worldwide cause of cancer-related death, there remains a paucity of effective treatments for advanced disease. The molecular mechanisms underlying the development of colorectal cancer include altered cell signaling and cell cycle regulation that may result from epigenetic modifications of gene expression and function. Acting as important transcriptional regulators of normal biological processes, zinc finger proteins also play key roles in regulating the cellular mechanisms underlying colorectal neoplasia. These actions impact cell differentiation and proliferation, epithelial–mesenchymal transition, apoptosis, homeostasis, senescence, and maintenance of stemness. With the goal of highlighting promising points of therapeutic intervention, we review the oncogenic and tumor suppressor roles of zinc finger proteins with respect to colorectal cancer tumorigenesis and progression. Full article
(This article belongs to the Special Issue Physiological and Pathological Functions of Zinc Finger Proteins)
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