Acute myeloid leukemia is mainly characterized by a complex and dynamic genomic instability. Next-generation sequencing has significantly improved the ability of diagnostic research to molecularly characterize and stratify patients. This detailed out...
DNA in dividing cells is prone to mutagenesis, with mutations making key contributions to human disease including cancer. The tumour suppressor gene TP53 is the most frequently mutated gene in human tumours. Here, we present a robust protocol for stu...
(1) Background: PTC124 (Ataluren) is an investigational drug for the treatment of nonsense mutation-mediated genetic diseases. With the exception of the TP53 tumor suppressor gene, there has been little research on cancers with nonsense mutation. By...
Personalized cancer medicine holds promise for the future of cancer treatment. One of the keys to success is the knowledge of exact molecular alterations that drive tumorigenesis in a given patient, so that a suitable targeted therapy can be selected...
Tumor suppressors play an important role in cancer pathogenesis and in the modulation of resistance to treatments. Loss of function of the proteins encoded by tumor suppressors, through genomic inactivation of the gene, disable all the controls that...
DNA damage is crucial for the emergence of cancer cells. If the DNA damage response is defective, the DNA damage is converted to fixed mutations. Some of these mutations drive tumorigenesis and are called driver mutations. However, the extent of cons...
Biomarker-driven targeted therapies are lacking for head and neck squamous cell carcinoma (HNSCC), which is common and lethal. Efforts to develop such therapies are hindered by a genomic landscape dominated by the loss of tumor suppressor function, i...
Myeloproliferative neoplasms (MPNs) constitute a group of disorders identified by an overproduction of cells derived from myeloid lineage. The majority of MPNs have an identifiable driver mutation responsible for cytokine-independent proliferative si...
Hotspot mutations in the NRAS gene are causative genetic events associated with the development of melanoma. Currently, there are no FDA-approved drugs directly targeting NRAS mutations. Previously, we showed that p38 acts as a tumor suppressor in vi...
The severe strain of citrus tristeza virus (CTV) causes quick decline of citrus trees. However, the CTV mild strain causes no symptoms and commonly presents in citrus trees. Viral suppressor of RNA silencing (VSR) plays an important role in the succe...
Ovarian seromucinous tumors (SMBTs) are relatively rare, and their carcinogenesis is largely unknown. In this study, the molecular features of SMBTs in Japan are assessed. DNA was extracted from microdissected paraffin-embedded sections from 23 SMBT...
Although hotspot mutations in isocitrate dehydrogenase (IDH) genes are associated with favorable clinical outcomes in glioma, CDKN2A/B homozygous deletion has been identified as an independent predicator of poor prognosis. Accordingly, the 2021 editi...
Probing the pathogenicity and functional consequences of mitochondrial DNA (mtDNA) mutations from patient’s cells and tissues is difficult due to genetic heteroplasmy (co-existence of wild type and mutated mtDNA in cells), occurrence of numerou...
Kirsten-RAS (KRAS) has been the target of drugs because it is the most mutated gene in human cancers. Because of the low affinity of drugs for KRAS mutations, it was difficult to target these tumor genes directly. We found a direct interaction betwee...
Breast cancer is the leading cause of cancer-related deaths in women. The aggressive breast cancer subtype is commonly linked to the genetic alterations in the TP53 tumor suppressor gene, predominantly the missense mutations. Robust experimental mode...
The Notch signaling pathway is a critical player in embryogenesis but also plays various roles in tumorigenesis, with both tumor suppressor and oncogenic activities. Mutations, deletions, amplifications, or over-expression of Notch receptors, ligands...
Malignant mesothelioma (MM), a rare and severe cancer, mainly caused as a result of past-asbestos exposure, is presently a public health concern. Current molecular studies aim to improve the outcome of the disease, providing efficient therapies based...
Retinoblastoma is a rare type of cancer, and its treatment, as well as diagnosis, is challenging, owing to mutations in the tumor-suppressor genes and lack of targeted, efficient, cost-effective therapy, exhibiting a significant need for novel approa...
Thyroid cancer is the most frequent endocrine malignancy and accounts for approximately 1% of all diagnosed cancers. A variety of mechanisms are involved in the transformation of a normal tissue into a malignant one. Loss of tumor-suppressor gene (TS...
Cancer is complex because of the critical imbalance in genetic regulation as characterized by both the overexpression of oncogenes (OGs), mainly through mutations, amplifications, and translocations, and the inactivation of tumor-suppressor genes (TS...
One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately...
In Caenorhabditis elegans, gap junctions couple cells of the somatic gonad with the germline to support germ cell proliferation and gametogenesis. A strong loss-of-function mutation (T239I) affects the second extracellular loop (EL2) of the somatic I...
In E. coli, transcriptional activation is often mediated by the C-terminal domain of RpoA, the α subunit of RNA polymerase. Random mutations that prevent activation of the arabinose PBAD promoter are clustered in the RpoA C-terminal domain (&al...
Neutral and adaptive mutations are key players in the evolutionary dynamics of proteins at molecular, cellular and organismal levels. Conversely, largely destabilizing mutations are rarely tolerated by evolution, although their occurrence in diverse...
The conformational heterogeneity of the p53 tumor suppressor, the wild-type (p53wt) and mutated forms, was investigated by a computational approach, including the modeling and all atoms of the molecular dynamics (MD) simulations. Four different punct...
The development of cancer is driven by genomic instability and mutations. In general, cancer develops via multiple steps. Each step involves the clonal evolution of cells with abrogated defense systems, such as cells with mutations in cancer-suppress...
Background: The ARF tumour suppressor plays a well-established role as a tumour suppressor, halting cell growth by both p53-dependent and independent pathways in several cellular stress response circuits. However, data collected in recent years chall...
Phosphatase and tensin homolog deleted on chromosome 10, or PTEN, is a well-characterized tumor suppressor with both lipid and protein phosphatase activities. PTEN is often downregulated by epigenetic mechanisms such as hypermethylation, which leads...
Pheochromocytomas and paragangliomas are rare tumors of neural crest origin. Their remarkable genetic diversity and high heritability have enabled discoveries of bona fide cancer driver genes with an impact on diagnosis and clinical management and ha...
The FBXW7 (F-box with 7 tandem WD40) protein encoded by the gene FBXW7 is one of the crucial components of ubiquitin ligase called Skp1-Cullin1-F-box (SCF) complex that aids in the degradation of many oncoproteins via the ubiquitin-proteasome system...
Higher plants exploit posttranscriptional gene silencing as a defense mechanism against virus infection by the RNA degradation system. Plant RNA viruses suppress posttranscriptional gene silencing using their encoded proteins. Three important motifs...
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy that is associated with a poor prognosis. The pathogenesis of MCC is not well understood, and despite a recent plethora of mutational analyses, we have yet to find a set...
(1) Background: Metallo-β-lactamases (MBLs) have raised concerns due to their ability to inactivate carbapenems and newer generation cephalosporins and the absence of clinically available MBL inhibitors. Their genes are often transferred horizon...
Conventional circulating tumor cell (CTC) detection technologies are restricted to large tumor cells (> white blood cells (WBCs)), or those unique carcinoma cells with double positive expression of surface epithelial cell adhesion molecule (EpCAM)...
P0 proteins encoded by poleroviruses Brassica yellows virus (BrYV) and Potato leafroll virus (PLRV) are viral suppressors of RNA silencing (VSR) involved in abolishing host RNA silencing to assist viral infection. However, other roles that P0 protein...
Emergent cancer drug resistance and further metastasis can mainly be attributed to altered expression levels and functional activities of multiple genes of cancer cells under chemotherapy. In response to challenge with anticancer drugs, enhanced cera...
A central challenge in cancer genomics is the systematic identification of single and cooperating tumor suppressor gene mutations driving cellular transformation and tumor progression in the absence of oncogenic driver mutation(s). Multiple in vitro...
Mutations in the tumor suppressor p53 (p53) promote cancer progression. This is mainly due to loss of function (LOS) as a tumor suppressor, dominant-negative (DN) activities of missense mutant p53 (mutp53) over wild-type p53 (wtp53), and wtp53-indepe...
The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor funct...
Forty years of research has proven beyond any doubt that p53 is a key regulator of many aspects of cellular physiology. It is best known for its tumor suppressor function, but it is also a regulator of processes important for maintenance of homeostas...
The fungal plant pathogen, Fusarium graminearum, contains two genes, FgCPK1 and FgCPK2, encoding the catalytic subunits of cAMP-dependent protein kinase A. FgCPK1 and FgCPK2 are responsible for most of the PKA activities and have overlapping function...
Tumor microenvironment (TME) is the immediate environment where cancer cells reside in a tumor. It is composed of multiple cell types and extracellular matrix. Microenvironments can be restrictive or conducive to the progression of cancer cells. Init...
Mutations in tumor suppressor genes often lead to cancerous phenotypes. Current treatments leverage signaling pathways that are often compromised by disease-derived deficiencies in tumor suppressors. P53 falls into this category as genetic mutations...
Ovarian cancer is the most lethal gynecological malignancy, with an alarmingly poor prognosis attributed to late detection and chemoresistance. Initially, most tumors respond to chemotherapy but eventually relapse due to the development of drug resis...
We previously showed that lipopolysaccharide (LPS) assembly requires the essential LapB protein to regulate FtsH-mediated proteolysis of LpxC protein that catalyzes the first committed step in the LPS synthesis. To further understand the essential fu...
The tumor suppressor p53 (TP53) is the most frequently mutated human gene. Mutations in TP53 not only disrupt its tumor suppressor function, but also endow oncogenic gain-of-function (GOF) activities in a manner independent of wild-type TP53 (wtp53)....
Background: BRCA1, BECN1 and TP53 are three tumor suppressor genes located on chromosome 17 and frequently found deleted, silenced, or mutated in many cancers. These genes are involved in autophagy, apoptosis, and drug resistance in ovarian cancer. H...
Background/Objectives: Type II ovarian cancer, including high-grade serous carcinoma (HGSC), is genetically unstable and exhibits frequent mutations in the tumor suppressor genes. Mutations of TP53 and BRCA1 genes have been associated with HGSC, whic...
29 November 2023
Tumor protein P53 (TP53) is an important tumor suppressor gene in humans. Under normal circumstances, TP53 can help repair mutated genes, or promote the death of cells with severe gene mutations (specifically, TP53 prevents cells from arrest in the G...
The Hedgehog receptor, Patched1 (PTCH1), is a well-known tumour suppressor. While the tumour suppressor’s activity is mostly ascribed to its function as a repressor of the canonical Smoothened/Gli pathway, its C-terminal domain (CTD) was report...
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