scholarly journals The Case of the Scribble Polarity Module in Asymmetric Neuroblast Division in Development and Tumorigenesis

2020 ◽  
Vol 21 (8) ◽  
pp. 2865
Author(s):  
Ana Carmena
Keyword(s):  
Epithelial Cell ◽  
Tumor Suppressor ◽  
Cell Polarity ◽  
Tumor Suppressor Genes ◽  
Asymmetric Division ◽  
Suppressor Genes ◽  
Epithelial Cell Polarity ◽  
Discs Large ◽  
Underlying Mechanisms

The Scribble polarity module is composed by Scribble (Scrib), Discs large 1 (Dlg1) and Lethal (2) giant larvae (L(2)gl), a group of highly conserved neoplastic tumor suppressor genes (TSGs) from flies to humans. Even though the Scribble module has been profusely studied in epithelial cell polarity, the number of tissues and processes in which it is involved is increasingly growing. Here we discuss the role of the Scribble module in the asymmetric division of Drosophila neuroblasts (NBs), as well as the underlying mechanisms by which those TSGs act in this process. Finally, we also describe what we know about the consequences of mutating these genes in impairing the process of asymmetric NB division and promoting tumor-like overgrowth.

The functional role of tumor suppressor genes in gliomas: Clues for future therapeutic strategies

Neurology ◽  
1998 ◽  
Vol 51 (5) ◽  
pp. 1250-1255 ◽  
Author(s):  
J. Fueyo ◽  
C. Gomez-Manzano ◽  
W. K. Alfred Yung ◽  
A. P. Kyritsis
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Functional Role ◽  
Therapeutic Strategies ◽  
Suppressor Genes

scholarly journals Electrostatic plasma membrane targeting contributes to Dlg function in cell polarity and tumorigenesis

Development ◽  
2021 ◽  
pp. dev.196956
Author(s):  
Juan Lu ◽  
Wei Dong ◽  
Yan Tao ◽  
Yang Hong
Keyword(s):  
Plasma Membrane ◽  
Tumor Suppressor ◽  
Epithelial Cells ◽  
Cell Polarity ◽  
Significant Role ◽  
Discs Large ◽  
Cortical Localization ◽  
Polarity Proteins ◽  
Positively Charged

Discs large (Dlg) is an essential polarity protein and a tumor suppressor originally characterized in Drosophila but is also well conserved in vertebrates. Like the majority of polarity proteins, plasma membrane (PM)/cortical localization of Dlg is required for its function in polarity and tumorigenesis, but the exact mechanisms targeting Dlg to PM remain to be fully elucidated. Here we show that, similar to the recently discovered polybasic polarity proteins such as Lgl and aPKC, Dlg also contains a positively charged polybasic domain that electrostatically binds the PM phosphoinositides PI4P and PI(4,5)P2. Electrostatic targeting by the polybasic domain contributes significantly to the PM localization of Dlg in follicular and early embryonic epithelial cells, and is crucial for Dlg to regulate both polarity and tumorigenesis. The electrostatic PM targeting of Dlg is controlled by a potential phosphorylation-dependent allosteric regulation of its polybasic domain, and is specifically enhanced by the interactions between Dlg and another basolateral polarity protein and tumor suppressor Scrib. Our studies highlight an increasingly significant role of electrostatic PM targeting of polarity proteins in regulating cell polarity.

scholarly journals The role of XPC protein deficiency in tobacco smoke-induced DNA hypermethylation of tumor suppressor genes

2013 ◽  
Vol 03 (04) ◽  
pp. 285-293 ◽  
Author(s):  
Gan Wang ◽  
Le Wang ◽  
Vanitha Bhoopalan ◽  
Yue Xi ◽  
Deepak K. Bhalla ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tobacco Smoke ◽  
Tumor Suppressor Genes ◽  
Protein Deficiency ◽  
Dna Hypermethylation ◽  
Suppressor Genes

scholarly journals Loss of Heterozygosity at the Ink4a/ArfLocus Facilitates Abelson Virus Transformation of Pre-B Cells

2000 ◽  
Vol 74 (20) ◽  
pp. 9479-9487 ◽  
Author(s):  
Justin Mostecki ◽  
Anne Halgren ◽  
Arash Radfar ◽  
Zohar Sachs ◽  
James Ravitz ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Suppressor ◽  
Loss Of Heterozygosity ◽  
Cell Lines ◽  
Tumor Suppressor Genes ◽  
Single Copy ◽  
Transformation Process ◽  
Suppressor Genes ◽  
Abelson Virus

ABSTRACT In many tumor systems, analysis of cells for loss of heterozygosity (LOH) has helped to clarify the role of tumor suppressor genes in oncogenesis. Two important tumor suppressor genes, p53 and the Ink4a/Arf locus, play central roles in the multistep process of Abelson murine leukemia virus (Ab-MLV) transformation. p53 and the p53 regulatory protein, p19Arf, are required for the apoptotic crisis that characterizes the progression of primary transformed pre-B cells to fully malignant cell lines. To search for other tumor suppressor genes which may be involved in the Ab-MLV transformation process, we used endogenous proviral markers and simple-sequence length polymorphism analysis to screen Abelson virus-transformed pre-B cells for evidence of LOH. Our survey reinforces the role of the p53-p19 regulatory pathway in transformation; 6 of 58 cell lines tested had lost sequences on mouse chromosome 4, including theInk4a/Arf locus. Consistent with this pattern, a high frequency of primary pre-B-cell transformants derived fromInk4a/Arf +/− mice became established cell lines. In addition, half of them retained the single copy of the locus when the transformation process was complete. These data demonstrate that a single copy of the Ink4a/Arf locus is not sufficient to fully mediate the effects of these genes on transformation.

scholarly journals Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Wen Zeng ◽  
Hanjun Dai ◽  
Ming Yan ◽  
Xiaojun Cai ◽  
Hong Luo ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Line ◽  
Tumor Suppressor Genes ◽  
Therapeutic Effects ◽  
Suppressor Genes ◽  
Recommended Treatment ◽  
Cycle Arrest ◽  
Induced Changes ◽  
Hyperphosphorylated Form

The epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones. Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the reexpression of silenced tumor suppressor genes. We investigated the effects of DAC treatment on the myeloid MDS cell line SKM-1 and investigated the role of FOXO3A, a potentially tumor-suppressive transcription factor, by silencing its expression prior to DAC treatment. We found that FOXO3A exists in an inactive, hyperphosphorylated form in SKM-1 cells, but that DAC both induces FOXO3A expression and reactivates the protein by reducing its phosphorylation level. Furthermore, we show that this FOXO3A activation is responsible for the DAC-induced differentiation of SKM-1 cells into monocytes, as well as for SKM-1 cell cycle arrest, apoptosis, and autophagy. Collectively, these results suggest that FOXO3A reactivation may contribute to the therapeutic effects of DAC in MDS.

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