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1.
ZMIZ proteins: partners in transcriptional regulation and risk factors for human disease.
Lomelí, H
Journal of molecular medicine (Berlin, Germany). 2022;(7):973-983
Abstract
Coregulator proteins interact with signal-dependent transcription factors to modify their transcriptional activity. ZMIZ1 and ZMIZ2 (zinc finger MIZ-type containing 1 and 2) are coregulators with nonredundant functions that share unique structural characteristics. Among other interacting domains, they possess a MIZ (Msx-interacting zinc finger) that relates them to members of the protein inhibitor of activated STAT (PIAS) family and provides them the capacity to function as SUMO E3 ligases. The ZMIZ proteins stimulate the activity of various signaling pathways, including the androgen receptor (AR), P53, SMAD3/4, WNT/β-catenin, and NOTCH1 pathways, and interact with the BAF chromatin remodeling complex. Due to their molecular versatility, ZMIZ proteins have pleiotropic effects and thus are important for embryonic development and for human diseases. Both have been widely associated with cancer, and ZMIZ1 has been very frequently identified as a risk allele for several autoimmune conditions and other disorders. Moreover, mutations in the coding region of the ZMIZ1 gene are responsible for a severe syndromic neurodevelopmental disability. Because the actions of coregulators are highly gene-specific, a better knowledge of the associations that exist between the function of the ZMIZ coregulators and human pathologies is expected to potentiate the use of ZMIZ1 and ZMIZ2 as new drug targets for diseases such as hormone-dependent cancers.
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2.
Nutritional Sensor REDD1 in Cancer and Inflammation: Friend or Foe?
Zhidkova, EM, Lylova, ES, Grigoreva, DD, Kirsanov, KI, Osipova, AV, Kulikov, EP, Mertsalov, SA, Belitsky, GA, Budunova, I, Yakubovskaya, MG, et al
International journal of molecular sciences. 2022;(17)
Abstract
Regulated in Development and DNA Damage Response 1 (REDD1)/DNA Damage-Induced Transcript 4 (DDIT4) is an immediate early response gene activated by different stress conditions, including growth factor depletion, hypoxia, DNA damage, and stress hormones, i.e., glucocorticoids. The most known functions of REDD1 are the inhibition of proliferative signaling and the regulation of metabolism via the repression of the central regulator of these processes, the mammalian target of rapamycin (mTOR). The involvement of REDD1 in cell growth, apoptosis, metabolism, and oxidative stress implies its role in various pathological conditions, including cancer and inflammatory diseases. Recently, REDD1 was identified as one of the central genes mechanistically involved in undesirable atrophic effects induced by chronic topical and systemic glucocorticoids widely used for the treatment of blood cancer and inflammatory diseases. In this review, we discuss the role of REDD1 in the regulation of cell signaling and processes in normal and cancer cells, its involvement in the pathogenesis of different diseases, and the approach to safer glucocorticoid receptor (GR)-targeted therapies via a combination of glucocorticoids and REDD1 inhibitors to decrease the adverse atrophogenic effects of these steroids.
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3.
Novel GRHL2 Gene Variant Associated with Hearing Loss: A Case Report and Review of the Literature.
Trebusak Podkrajsek, K, Tesovnik, T, Bozanic Urbancic, N, Battelino, S
Genes. 2021;(4)
Abstract
In contrast to the recessive form, hearing loss inherited in a dominant manner is more often post-lingual and typically results in a progressive sensorineural hearing loss with variable severity and late onset. Variants in the GRHL2 gene are an extremely rare cause of dominantly inherited hearing loss. Genetic testing is a crucial part of the identification of the etiology of hearing loss in individual patients, especially when performed with next-generation sequencing, enabling simultaneous analysis of numerous genes, including those rarely associated with hearing loss. We aimed to evaluate the genetic etiology of hearing loss in a family with moderate late-onset hearing loss using next-generation sequencing and to conduct a review of reported variants in the GRHL2 gene. We identified a novel disease-causing variant in the GRHL2 gene (NM_024915: c.1510C>T; p.Arg504Ter) in both affected members of the family. They both presented with moderate late-onset hearing loss with no additional clinical characteristics. Reviewing known GRHL2 variants associated with hearing loss, we can conclude that they are more likely to be truncating variants, while the associated onset of hearing loss is variable.
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4.
Zinc finger proteins: insights into the transcriptional and post transcriptional regulation of immune response.
Rakhra, G, Rakhra, G
Molecular biology reports. 2021;(7):5735-5743
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Abstract
BACKGROUND Zinc finger proteins encompass one of the unique and large families of proteins with diversified biological functions in the human body. These proteins are primarily considered to be DNA binding transcription factors; however, owing to the diverse array of zinc-finger domains, they are able to interact with molecules other than DNA like RNA, proteins, lipids and PAR (poly-ADP-ribose). Evidences from recent scientific studies have provided an insight into the potential functions of zinc finger proteins in immune system regulation both at the transcriptional and post transcriptional level. However, the mechanism and importance of zinc finger proteins in the regulation of immune response is not very well defined and understood. This review highlights in detail the importance of zinc finger proteins in the regulation of immune system at transcriptional and post transcriptional level. CONCLUSION Different types of zinc finger proteins are involved in immune system regulation and their mechanism of regulation is discussed herewith.
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5.
Metabolic engineering: Towards water deficiency adapted crop plants.
Yoshida, T, Yamaguchi-Shinozaki, K
Journal of plant physiology. 2021;:153375
Abstract
Water deficiency caused by drought is one of the severe environmental conditions limiting plant growth, development, and yield. In this review article, we will summarize the changes in transcription, metabolism, and phytohormones under drought stress conditions and show the key transcription factors in these processes. We will also highlight the recent attempts to enhance stress tolerance without growth retardation and discuss the perspective on the development of stress adapted crops by engineering transcription factors.
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6.
Progress on the GntR family transcription regulators in bacteria.
Liu, GF, Wang, XX, Su, HZ, Lu, GT
Yi chuan = Hereditas. 2021;(1):66-73
Abstract
In bacteria, GntR family transcription regulators are the widespread family of transcription factors. Members of this family consist of two functional domains, a conserved N-terminal DNA-binding domain that contains a typical helix-turn-helix (HTH) motif and a C-terminal effector-binding or oligomerization domain. Usually, the amino acid sequences of N-terminal DNA-binding domains are highly conserved, but differ in the C-terminal effector-binding or oligomerization domains. In the past several decades, many GntR family transcription regulators have been characterized in a number of bacteria. These regulators control a variety of cellular processes such as cell motility, glucose metabolism, bacterial resistance, pathogenesis and virulence. In this review, we summarized the discovery, C-terminal domains, biological function and regulation mode of GntR family transcription regulators. This review will help researchers to obtain more knowledge about the functions and mechanisms of the GntR family transcriptional regulatory factors.
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7.
Role of ZBTB7A zinc finger in tumorigenesis and metastasis.
Singh, AK, Verma, S, Kushwaha, PP, Prajapati, KS, Shuaib, M, Kumar, S, Gupta, S
Molecular biology reports. 2021;(5):4703-4719
Abstract
The zinc finger and BTB (broad-complex, tramtrack and bric a brac) domain containing protein 7A (ZBTB7A) is a pleiotropic transcription factor that plays an important role in various stages of cell proliferation, differentiation, and other developmental processes. ZBTB7A is a member of the POK family that directly and specifically binds to short DNA recognition sites located near their target genes thereby acting as transcriptional activator or repressor. ZBTB7A overexpression has been associated with tumorigenesis and metastasis in various human cancer types, including breast, prostate, lung, ovarian, and colon cancer. However in some instances downregulation of ZBTB7A results in tumor progression, suggesting its role as a tumor suppressor. ZBTB7A is involved with complicated regulatory networks which include protein-protein and protein-nucleic acid interactions. ZBTB7A involvement in cancer progression and metastasis is perhaps enabled through the regulation of various signaling pathways depending on the type and genetic context of cancer. The association of ZBTB7A with other proteins affects cancer aggressiveness, therapeutic resistance and clinical outcome. This review focuses on the involvement of ZBTB7A in various signaling pathways and its role in cancer progression. We will also review the literature on ZBTB7A and cancer which could be potentially explored for its therapeutic implications.
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8.
Genome-wide identification of Pistacia R2R3-MYB gene family and function characterization of PcMYB113 during autumn leaf coloration in Pistacia chinensis.
Song, X, Yang, Q, Liu, Y, Li, J, Chang, X, Xian, L, Zhang, J
International journal of biological macromolecules. 2021;:16-27
Abstract
Pistacia chinensis is known for its biodiesel production. Several varieties of this plant have leaves that produce anthocyanin, which is responsible for their reddish coloration in autumn. This reddish hue is what makes them useful as ornamental plants. However, the mechanism of anthocyanin accumulation during autumn leaf coloration remains unclear. R2R3-MYB proteins reportedly regulated anthocyanin biosynthesis in many plant species. Here, we performed a genome-wide analysis and expression profiles of R2R3-MYB transcription factor in Pistacia. A total of 158 R2R3-MYB proteins were identified and grouped into 32 clades. Combining the data from RNA-seq and qRT-PCR, one key gene, EVM0016534, was screened and identified to have the highest correlation with anthocyanin accumulation. It was named PcMYB113 due to its sequence similarity to AtMYB113 and it could bind to the promoter of PcF3H. Furthermore, ectopic expression of PcMYB113 in Arabidopsis promoted the accumulation of anthocyanin in the seed coat, cotyledon, and mature leaves, thus confirming the function of PcMYB113 in anthocyanin biosynthesis. In addition, PcMYB113 had a specifically higher expression in senesced red leaves than in mature green leaves and young red leaves in P. chinensis, thereby suggesting the potential role of PcMYB113 in promoting anthocyanin biosynthesis during autumn leaf coloration. These findings enrich our understanding of the function of R2R3-MYB genes in anthocyanin biosynthesis and autumn leaf coloration.
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A novel homozygous exon2 deletion of TRIM32 gene in a Chinese patient with sarcotubular myopathy: A case report and literature review.
Wei, XJ, Miao, J, Kang, ZX, Gao, YL, Wang, ZY, Yu, XF
Bosnian journal of basic medical sciences. 2021;(4):495-500
Abstract
Sarcotubular myopathy (STM) is a rare autosomal recessive myopathy caused by TRIM32 gene mutations. It is predominantly characterized by the weakness of the proximal limb and mild to moderate elevation of creatine kinase (CK) levels. In this study, we describe a 50-year-old Chinese man who exhibited a proximal-to-distal weakness in the muscles of the lower limbs and who had difficulty standing up from a squat position. The symptoms gradually became more severe. He denied a history of cognitive or cardiological problems. The patient's parents and children were healthy. Histopathological examination revealed dystrophic changes and irregular slit-shaped vacuoles containing amorphous materials. Whole-exome sequencing consisting of protein-encoding regions of 19,396 genes was performed, the results of which identified one novel homozygous 2kb deletion chr9.hg19: g.119460021_119461983del (exon2) in the TRIM32 gene. This was confirmed at the homozygous state with quantitative real-time PCR. Here, we present a Chinese case of STM with one novel mutation in TRIM32 and provide a brief summary of all known pathogenic mutations in TRIM32.
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10.
MiT Family Transcriptional Factors in Immune Cell Functions.
Kim, S, Song, HS, Yu, J, Kim, YM
Molecules and cells. 2021;(5):342-355
Abstract
The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmia-associated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.