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Precision medicine in multiple sclerosis
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
The forkhead/winged helix gene (FOXP3) is involved in MS (Gholami et al., 2017). Interferon regulatory factor 5 (IRF5) has been validated as the multiple sclerosis risk gene (Vandenbroeck et al., 2011). The SLC9A9 gene is implicated in MS (Esposito et al., 2015). Several genes (Table 15.2) have been associated with MS (Oksenberg and Hauser, 2008).
The Premature Aging Characteristics of RecQ Helicases
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Christ Ordookhanian, Taylor N. Dennis, J. Jefferson P. Perry
The central component of RecQ helicases is an architecture that belongs to the larger Superfamily 2 (SF2) helicases, with some features unique to RecQ proteins, consisting of helicase domains 1 and 2 (HD1, HD2) and a RecQ C-terminal (RQC) region (Figure 10.1). Within HD1 & 2 reside the classical seven-helicase sequence motifs (I, Ia, II, III, IV, V, and VI) that are known to couple ATP binding and hydrolysis with DNA unwinding. Mutation of these motifs can disrupt RecQ function [17] where a mutation within these motifs of WRN protein resulted in a Werner phenotype in mice tail-derived fibroblasts [18]. The Walker A and B Motifs (Motifs I and II) directly bind to ATP (or ATP analogs in the RecQ crystal structures) [19], as observed in the SF1 & 2 helicases, but there is also an extra region conserved in RecQs termed “Motif 0” that is a pocket that preferentially accommodates the adenine base of ATP. This pocket is similar to a pocket in RNA DEAD-box helicases known as the Q motif, suggesting a potential evolutionary link between these two classes of helicases. X-ray crystallography studies on several RecQ helicase structures, including human RecQ1 [20] and human BLM [21,22], have revealed that the RQC region is integral to the helicase core. This region is composed of a Zn2+-binding region and a winged-helix domain. The Zn2+ ion is chelated by four conserved cysteine residues, the mutation of which disrupts RecQ helicase function, and causes BS when mutated in BLM [23]. The winged-helix domain has high affinity for DNA likely providing substrate specificities, in addition to unique protein partner interactions for the RecQs.
Foxo3a-Mediated DNMT3B Impedes Cervical Cancer Cell Proliferation and Migration Capacities through Suppressing PTEN Promoter Methylation
Published in Journal of Investigative Surgery, 2023
Hongying Li, Yuqin Yuan, Hong Dong, Tinghui Wang, Dunlan Zhang, Limin Zhou, Lu Chen, Xueyan He
Like most other cancers, cervical cancer is also linked with the constitutive activation of growth factors and gene mutations-induced pro-survival signaling pathways [6]. Epigenetic changes exert functions in cervical cancer development, and DNA methylation is an epigenetic modification in which cells modulate gene transcription and expression [7]. Forkhead/winged helix box (FOXO)3a, belongs to the class of FOXO transcription factors, acts as an anti-tumor factor implicated in different cellular processes [8]. FOXO3a is modified by acetylation, ubiquitination, and phosphorylation, which, on the contrary, impacts the transcriptional activity and stability, and unclear/cytoplasm shuttling [9,10]. As previously demonstrated, the suppressive role of FoxO3a is realized through controlling the gene expression involved in oxidative stress, apoptosis, as well as autophagy [11,12]. It is reported that FOXO3a plays a part in cervical cancer cells [13], while its inner mechanism remains to be undefined. Yang et al. have supported that FOXO3a negatively modulates the DNA methyltransferase 3 beta (DNMT3B) promoter activity [13]. More interestingly, Li et al. in their work have demonstrated that DNMT3B expression has a correlation with PTEN level, and there is a positive relationship between DNMT3B overexpression and PTEN loss [14]. Based on this, we conducted this work to elucidate the possible molecular mechanism of Foxo3a-mediated DNMT3B in the proliferation and migration capabilities of cervical cancer cells via mediating the PTEN promoter methylation.
STOX1 promotor region -922 T > C polymorphism is associated with Early-Onset preeclampsia
Published in Journal of Obstetrics and Gynaecology, 2022
Seyda Akin, Ergun Pinarbasi, Aslihan Esra Bildirici, Nilgun Cekin
It was put forward that the region of approximately 3,600 bp in intron 1, showing a variable methylation pattern in the STOX1 gene, reduces STOX1 expression. Also, this variable methylation is not of parental origin and that the Y153H polymorphism regulates STOX1 expression (van Dijk et al.2010). Our results suggesting that the same interpretation can be made for the rs884181 in promotor region and also brings a different question to mind; ‘Whether these two mutations is the susceptibility to PE the highest or not?’. Y153H variant is found in the winged helix domain and known to be highly susceptible to mutation (van Dijk et al.2005). This information encapsulates that the relationship between the two variations should be elucidated and their contribution to the PE phenotype should be examined.
Assessment of CEP55, PLK1 and FOXM1 expression in patients with bladder cancer in comparison with healthy individuals
Published in Cancer Investigation, 2018
Saman Seyedabadi, Massoud Saidijam, Rezvan Najafi, Seyed Habibollah Mousavi-Bahar, Mohammad Jafari, Sajjad MohammadGanji, Ali Mahdavinezhad
Forkhead box protein M1 (FOXM1) belongs to the super family of transcription factors all of which have a conserved domain attached to the DNA (Winged helix). FOXM1 regulates a large number of gene expression by binding to the consensus sequence of TAAACA (7,8). FOXM1 over-expression is observed in many cancers such as prostate, brain, breast, lung, colon, pancreas, skin, ovary, and nervous system. However, the exact role and molecular mechanism of FOXM1 in BC is vague (9). FOXM1 is one of the rare genes that show increased expression in early stages of cancer (7,10). FOXM1 regulates the expression of several genes such as cdc25B, cyclinB, AuroraB kinase, polo-like kinase 1 (PLK1), and CENP (A, B, and C) (7).