<i>In silico</i>functional and tumor suppressor role of hypothetical protein PCNXL2 with regulation of the Notch signaling pathway

Naveed, Muhammad; Imran, Komal; Mushtaq, Ayesha; Mumtaz, Abdul Samad; Janjua, Hussnain Ahmed; Khalid, Nauman

doi:10.1039/c8ra00589c

Cited by 9 publications

(3 citation statements)

References 66 publications

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“…When activated by membrane-bound delta or Jagged ligands, the receptors are proteolytically cleaved by a metalloprotease and γ-secretase to generate two fragments: the extracellular domain of NOTCH (NECD) and NICD [41, 42]. The soluble NICD is released into the cytoplasm [43]. Direct engagement of TRAF6 in AKT signaling [44, 45] can activate AKT during the growth of NPC.…”

Section: Discussionmentioning

confidence: 99%

NOTCH2 negatively regulates metastasis and epithelial-Mesenchymal transition via TRAF6/AKT in nasopharyngeal carcinoma

Zou

Yang

Huang

et al. 2019

J Exp Clin Cancer Res

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BackgroundClinically, distant metastasis after primary treatment remains a key problem in nasopharyngeal carcinoma (NPC). Thus, identification of the underlying mechanisms and development of novel therapeutic strategies are urgently needed. NOTCH has been shown to function as a tumor promotor that enhances angiogenesis, cancer invasion and metastasis in NPC. However, the precise roles of the four individual NOTCH receptors and their mechanisms of action are unclear.MethodsWe used Western blot analysis, immunofluorescence, immunohistochemical analysis, phalloidin staining, mouse tumor metastatic dissemination models, gene set enrichment analysis, immunoprecipitation assays and a series of functional assays to determine the potential role of NOTCH2 in regulating NPC metastasis.ResultsNOTCH2 expression in the NPC tissues of patients with cervical lymph node metastasis was lower than that of patients without cervical lymph node metastasis. Correspondingly, NOTCH2 expression was low in metastatic and poorly differentiated NPC cells. NOTCH2 expression correlated negatively with survival time in patients with NPC. Suppression of NOTCH2 expression promoted NPC cell metastasis, whereas NOTCH2 overexpression inhibited this process. Furthermore, NOTCH2 attenuated the TRAF6–AKT signaling axis via an interaction between the NOTCH2 intracellular domain (N2ICD) and TRAF6, which inhibited epithelial–mesenchymal transition (EMT) and eventually suppressed NPC metastasis.ConclusionsThese findings reveal that loss of NOTCH2 activates the TRAF6/AKT axis and promotes metastasis in NPC, suggesting that NOTCH2 may represent a therapeutic target for the treatment of NPC.

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Section: Discussionmentioning

confidence: 99%

NOTCH2 negatively regulates metastasis and epithelial-Mesenchymal transition via TRAF6/AKT in nasopharyngeal carcinoma

Zou

Yang

Huang

et al. 2019

J Exp Clin Cancer Res

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“…An example of a tumor suppressor gene is PCNXL2 or protein pecanex-like protein 2 Homo sapiens that encodes multi-pass transmembrane proteins that regulate the Notch signaling pathway. 67 Its activity to regulate Notch signaling occurs when protons are transported across the membrane thereby providing adequate membrane potential that would be enough to activate y-secretase. Y-Secretase then liberates the Notch intracellular domain (NICD) from its receptor to the inside of the cell.…”

Section: Molecular Differencesmentioning

confidence: 99%

Molecular basis of sex differences in cancer: Perspective from Asia

Ornos¹,

Cando²,

Catral³

et al. 2023

iScience

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“…Bioinformatics is used to explore common genetic bases between T2D and AD. For instance, role of an hypothetical protein PCNXL2 involved in tumor suppression was analysed based on its functional and in-silico study [33]. Bioinformatics came into play as HaploReg (http://compbio.mit.edu/HaploReg) that analyse SNPs.…”

Section: Bioinformatics and Health Care Developmentmentioning

confidence: 99%

Emergence of in-silico biology in desperate spheres of life sciences in Pakistan

Naveed¹,

Amin

Sadia

et al. 2019

PAB

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Bioinformatics, a multidisciplinary field works in collaboration with biological sciences for analysis, prediction and storage of biological data in form of databases. In innovative world of scientific technology, Pakistan is playing its crucial role in development of new era of escience. Main objective of this review is to highlight bioinformatics applications and its significant role in progress of e-science in Pakistan. In Pakistan, numerous applications such as gene target approaches in agriculture, food industries and 3-dimensional structure analysis of protein have been revealed, where every aspect of nucleic acids processing can be observed. With these advancements, disease diagnosis has now become easy, providing a platform for drug development and enormous jobs for talented ones to make a history in bioinformatics. Similarly, numerous organizations are also taking part in Next Generation Sequencing (NGS) technology and different nationwide companies. However, bioinformatics also faces challenges in data collection and web designing. But introduction of innovative researches has led to formation of highly applicable e-technology of recent era. Hence, this approach has taken primacy to diagnose diseases as cancer. It makes a tremendous distinction in e-science where computer-aided drug design (CADD) gives a ray of hope for many diseased people. Moreover, comprehensive study of human genetics also reveals invention of specified drugs and various biomarkers to discriminate among every single genetic disease. Regardless of various hurdles, scientific transformations in very field related to bioinformatics will help us to take Pakistan beyond skylines and to stand with high tech world association.

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In silicofunctional and tumor suppressor role of hypothetical protein PCNXL2 with regulation of the Notch signaling pathway

Abstract: Since the last decade, various genome sequencing projects have led to the accumulation of an enormous set of genomic data; however, numerous protein-coding genes still need to be functionally characterized.

Cited by 9 publications

References 66 publications

NOTCH2 negatively regulates metastasis and epithelial-Mesenchymal transition via TRAF6/AKT in nasopharyngeal carcinoma

NOTCH2 negatively regulates metastasis and epithelial-Mesenchymal transition via TRAF6/AKT in nasopharyngeal carcinoma

Molecular basis of sex differences in cancer: Perspective from Asia

Emergence of in-silico biology in desperate spheres of life sciences in Pakistan

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