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SP/KLF Transcription Factors in the Homeostasis and Disease Progression
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SP/KLF Transcription Factors in the Homeostasis and Disease Progression

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

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 7680

Special Issue Editor

Dr. Agnieszka B. Bialkowska

E-Mail Website
Guest Editor
Department of Medicine, Renaissance School of Medicine at Stony Brook University, 101 Nicolls Road, Stony Brook, NY 11794, USA
Interests: transcription factors; Krüppel-like factor 4 (KLF4); Krüppel-Like Factor 5 (KLF5); intestinal biology; injury; inflammation; pancreatic neoplasia; pancreatic cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Specificity proteins (SPs) and Krüppel-like factors (KLFs) comprise a family of transcription factors (SP/KLF) regulating fundamental biological processes, including stemness, proliferation, apoptosis, regeneration, migration, and inflammation, in a wide variety of cell types and organisms. Structurally, these transcriptional factors are characterized by a highly conserved triple zinc-finger motif in their carboxyl-terminal domain. SP/KLF members preferentially bind to GC-rich regions of DNA and function as transcriptional activators and/or repressors. This transcriptional control regulates homeostasis and tumor initiation, promotion, and progression. Thus, many SP/KLF members are tumor suppressors and/or oncogenes. Since the identification of SP1 as a eukaryotic transcriptional factor binding to the promoter of SV40 (1983), understanding of the role of the SP/KLF family of transcriptional factors has grown tremendously, and their importance should not be underestimated. Recent technical and technological developments in novel animal models as well as molecular and cellular techniques, including RNA-seq, ATAC-seq, scRNA-seq, and in vitro 3D organoid culture, have allowed for more comprehensive analyses of SP/KLF family members and their function. This Special Issue focuses on recent progress in understanding the role of SP/KLF members in regulating embryogenesis and development, maintaining homeostasis, and during disease development and progression.

Dr. Agnieszka B. Bialkowska
Guest Editor

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

  • specificity protein
  • Krüppel-like factor
  • homeostasis
  • inflammation
  • pathophysiology
  • tumorigenesis

Published Papers (3 papers)

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Review

29 pages, 2219 KiB  
Review
The Role of Krüppel-like Factors in Pancreatic Physiology and Pathophysiology
by Michael Giarrizzo, Joseph F. LaComb and Agnieszka B. Bialkowska
Int. J. Mol. Sci. 2023, 24(10), 8589; https://doi.org/10.3390/ijms24108589 - 11 May 2023
Viewed by 2275
Abstract
Krüppel-like factors (KLFs) belong to the family of transcription factors with three highly conserved zinc finger domains in the C-terminus. They regulate homeostasis, development, and disease progression in many tissues. It has been shown that KLFs play an essential role in the endocrine [...] Read more.
Krüppel-like factors (KLFs) belong to the family of transcription factors with three highly conserved zinc finger domains in the C-terminus. They regulate homeostasis, development, and disease progression in many tissues. It has been shown that KLFs play an essential role in the endocrine and exocrine compartments of the pancreas. They are necessary to maintain glucose homeostasis and have been implicated in the development of diabetes. Furthermore, they can be a vital tool in enabling pancreas regeneration and disease modeling. Finally, the KLF family contains proteins that act as tumor suppressors and oncogenes. A subset of members has a biphasic function, being upregulated in the early stages of oncogenesis and stimulating its progression and downregulated in the late stages to allow for tumor dissemination. Here, we describe KLFs’ function in pancreatic physiology and pathophysiology. Full article
(This article belongs to the Special Issue SP/KLF Transcription Factors in the Homeostasis and Disease Progression)
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22 pages, 3625 KiB  
Review
Specificity Proteins (Sp) and Cancer
by Stephen Safe
Int. J. Mol. Sci. 2023, 24(6), 5164; https://doi.org/10.3390/ijms24065164 - 8 Mar 2023
Cited by 5 | Viewed by 1845
Abstract
The specificity protein (Sp) transcription factors (TFs) Sp1, Sp2, Sp3 and Sp4 exhibit structural and functional similarities in cancer cells and extensive studies of Sp1 show that it is a negative prognostic factor for patients with multiple tumor types. In this review, the [...] Read more.
The specificity protein (Sp) transcription factors (TFs) Sp1, Sp2, Sp3 and Sp4 exhibit structural and functional similarities in cancer cells and extensive studies of Sp1 show that it is a negative prognostic factor for patients with multiple tumor types. In this review, the role of Sp1, Sp3 and Sp4 in the development of cancer and their regulation of pro-oncogenic factors and pathways is reviewed. In addition, interactions with non-coding RNAs and the development of agents that target Sp transcription factors are also discussed. Studies on normal cell transformation into cancer cell lines show that this transformation process is accompanied by increased levels of Sp1 in most cell models, and in the transformation of muscle cells into rhabdomyosarcoma, both Sp1 and Sp3, but not Sp4, are increased. The pro-oncogenic functions of Sp1, Sp3 and Sp4 in cancer cell lines were studied in knockdown studies where silencing of each individual Sp TF decreased cancer growth, invasion and induced apoptosis. Silencing of an individual Sp TF was not compensated for by the other two and it was concluded that Sp1, Sp3 and Sp4 are examples of non-oncogene addicted genes. This conclusion was strengthened by the results of Sp TF interactions with non-coding microRNAs and long non-coding RNAs where Sp1 contributed to pro-oncogenic functions of Sp/non-coding RNAs. There are now many examples of anticancer agents and pharmaceuticals that induce downregulation/degradation of Sp1, Sp3 and Sp4, yet clinical applications of drugs specifically targeting Sp TFs are not being used. The application of agents targeting Sp TFs in combination therapies should be considered for their potential to enhance treatment efficacy and decrease toxic side effects. Full article
(This article belongs to the Special Issue SP/KLF Transcription Factors in the Homeostasis and Disease Progression)
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40 pages, 2651 KiB  
Review
Specificity Proteins (SP) and Krüppel-like Factors (KLF) in Liver Physiology and Pathology
by Veera Ganesh Yerra and Konstantinos Drosatos
Int. J. Mol. Sci. 2023, 24(5), 4682; https://doi.org/10.3390/ijms24054682 - 28 Feb 2023
Cited by 4 | Viewed by 3177
Abstract
The liver acts as a central hub that controls several essential physiological processes ranging from metabolism to detoxification of xenobiotics. At the cellular level, these pleiotropic functions are facilitated through transcriptional regulation in hepatocytes. Defects in hepatocyte function and its transcriptional regulatory mechanisms [...] Read more.
The liver acts as a central hub that controls several essential physiological processes ranging from metabolism to detoxification of xenobiotics. At the cellular level, these pleiotropic functions are facilitated through transcriptional regulation in hepatocytes. Defects in hepatocyte function and its transcriptional regulatory mechanisms have a detrimental influence on liver function leading to the development of hepatic diseases. In recent years, increased intake of alcohol and western diet also resulted in a significantly increasing number of people predisposed to the incidence of hepatic diseases. Liver diseases constitute one of the serious contributors to global deaths, constituting the cause of approximately two million deaths worldwide. Understanding hepatocyte transcriptional mechanisms and gene regulation is essential to delineate pathophysiology during disease progression. The current review summarizes the contribution of a family of zinc finger family transcription factors, named specificity protein (SP) and Krüppel-like factors (KLF), in physiological hepatocyte functions, as well as how they are involved in the onset and development of hepatic diseases. Full article
(This article belongs to the Special Issue SP/KLF Transcription Factors in the Homeostasis and Disease Progression)
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