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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.
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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4.
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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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.
Spanning the gap: unraveling RSC dynamics in vivo.
Neumann, H, Wilkins, BJ
Current genetics. 2021;(3):399-406
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Abstract
Multiple reports over the past 2 years have provided the first complete structural analyses for the essential yeast chromatin remodeler, RSC, providing elaborate molecular details for its engagement with the nucleosome. However, there still remain gaps in resolution, particularly within the many RSC subunits that harbor histone binding domains.Solving contacts at these interfaces is crucial because they are regulated by posttranslational modifications that control remodeler binding modes and function. Modifications are dynamic in nature often corresponding to transcriptional activation states and cell cycle stage, highlighting not only a need for enriched spatial resolution but also temporal understanding of remodeler engagement with the nucleosome. Our recent work sheds light on some of those gaps by exploring the binding interface between the RSC catalytic motor protein, Sth1, and the nucleosome, in the living nucleus. Using genetically encoded photo-activatable amino acids incorporated into histones of living yeast we are able to monitor the nucleosomal binding of RSC, emphasizing the regulatory roles of histone modifications in a spatiotemporal manner. We observe that RSC prefers to bind H2B SUMOylated nucleosomes in vivo and interacts with neighboring nucleosomes via H3K14ac. Additionally, we establish that RSC is constitutively bound to the nucleosome and is not ejected during mitotic chromatin compaction but alters its binding mode as it progresses through the cell cycle. Our data offer a renewed perspective on RSC mechanics under true physiological conditions.
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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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The interplay between ABA/ethylene and NAC TFs in tomato fruit ripening: a review.
Kou, X, Zhou, J, Wu, CE, Yang, S, Liu, Y, Chai, L, Xue, Z
Plant molecular biology. 2021;(3):223-238
Abstract
This review contains functional roles of NAC transcription factors in the transcriptional regulation of ripening in tomato fruit, describes the interplay between ABA/ethylene and NAC TFs in tomato fruit ripening. Fruit ripening is regulated by a complex network of transcription factors (TFs) and genetic regulators in response to endogenous hormones and external signals. Studying the regulation of fruit ripening has important significance for controlling fruit quality, enhancing nutritional value, improving storage conditions and extending shelf-life. Plant-specific NAC (named after no apical meristem (NAM), Arabidopsis transcription activator factor 1/2 (ATAF1/2) and Cup-shaped cotyledon (CUC2)) TFs play essential roles in plant development, ripening and stress responses. In this review, we summarize the recent progress on the regulation of NAC TFs in fruit ripening, discuss the interactions between NAC and other factors in controlling fruit development and ripening, and emphasize how NAC TFs are involved in tomato fruit ripening through the ethylene and abscisic acid (ABA) pathways. The signaling network regulating ripening is complex, and both hormones and individual TFs can affect the status or activity of other network participants, which can alter the overall ripening network regulation, including response signals and fruit ripening. Our review helps in the systematic understanding of the regulation of NAC TFs involved in fruit ripening and provides a basis for the development or establishment of complex ripening regulatory network models.
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9.
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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10.
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.