Regulators of Signal Transduction: Families of GTP-Binding Proteins
Robert I. Glazer in Developments in Cancer Chemotherapy, 2019
The rho genes are a family of evolutionarily conserved genes with 35% amino acid homology to ras. These genes have been detected in man, rats, Aplysia, and yeast.105,106 The yeast S. cerevisiae contains two genes termed RHO1 and RHO2, which are 53% identical to each other. Gene disruption experiments revealed that RHO1 is required for cell viability while RHO2 is not an essential gene. A point mutation in RHO1, analogous to a transforming mutation in ras, resulted in a dominant allele which prevented sporulation. This is very reminiscent of the situation for ras in yeast in which disruption of both RAS1 and RAS2 prevents sporulation. Furthermore, Kataoka et al.89 report that introduction of a chimeric human/yeast RAS2val12 gene (analogous to a transforming mutation in ras) under control of the GAL10 promoter results in the loss of cell viability even in cells containing intact endogenous RAS genes. Somewhat surprisingly, the lethality caused by RHO1 gene disruption cannot be suppressed by the introduction of a gene encoding the catalytic subunit of cAMP-dependent protein kinase or the gene for RAS2val19.106 This demonstrates that the ras and rho proteins are involved in the regulation of distinct biochemical pathways in yeast. Clearly then the rho protein(s) have functions independent of adenylate cyclase. What those functions may be remain unknown.
Head and Neck Cancers
Peter G. Shields in Cancer Risk Assessment, 2005
Assays that measure cellular DNA repair are now being applied in population studies to investigate the association between DNA repair and susceptibility to cancer. Generally, cellular responses to DNA damage fall into three major categories: direct reversal of damage, e.g., enzymatic photore activation; excision of damage by BER or NER; and postreplica-tion repair, namely, MMR and HRR (3). While the presence of only one unrepaired DNA lesion can block the transcription of an essential gene (81,82), there is a wide range of repair ability in the general population (83,84), with xeroderma pigmentosum (XP) patients representing the lowest end of the repair spectrum (85). Because there is a shortage of target tissues for laboratory experiments, peripheral blood lymphocytes have been used extensively as surrogate tissues (83,86).
The rho Gene Family
Juan Carlos Lacal, Frank McCormick in The ras Superfamily of GTPases, 2017
Two different members of the rho gene family have been isolated from Saccharomyces cerevisiae designated as RHOl and RH02, which are 53% homologous to each other.13 RHOl is also 70% identical to the Aplysia gene. Genetic experiments demonstrate that RHOl is an essential gene in yeast while RH02 is not required for cell viability. Overexpression of the catalytic subunit of the cAMP-dependent protein kinase or RAS-Val19, both capable of suppressing lethality of RAS deletions in yeast, does not suppress the lethality of a RHOl mutation suggesting that ras and rho genes function in independent pathways in yeast.
Tumor-targeting oncolytic virus elicits potent immunotherapeutic vaccine responses to tumor antigens
Published in OncoImmunology, 2020
Yong Luo, Chaolong Lin, Yidi Zou, Fei Ju, Wenfeng Ren, Yanhua Lin, Yale Wang, Xiaoxuan Huang, Huiling Liu, Zeng Yu, Pingguo Liu, Guowei Tan, Quan Yuan, Jun Zhang, Chenghao Huang, Ningshao Xia
Herpes Simplex Virus type I (HSV-1) offers particular advantages for use as an oncolytic vector in cancer therapy.15 We therefore undertook a stepwise design and development strategy to create a novel effective HSV-1 agent. First, ICP0 and ICP34.5, which are essential for HSV-1 replication in nondividing cells (normal cells) but are dispensable in rapidly dividing cells (tumor cells), were both deleted to make a better replication-selective and attenuated oncolytic virus. ICP0 is needed to stimulate translation of viral mRNA in quiescent cells and plays a key role in blocking IFN-induced inhibition of viral infection,16 so ICP0-null HSV-1 replicates more efficiently in tumor cells than in normal cells. ICP34.5 intercepts the interferon-induced PKR-mediated block to virus replication, which is usually disabled in tumor cells, thereby allowing ICP34.5-null HSV-1 mutants to proceed with viral infection.17 The deletion of ICP34.5 gene also can significantly reduce the neurotoxicity of virus to host.18 Second, the telomerase reverse transcriptase (hTERT) promoter, which is transcriptionally active in tumor cells, has been utilized to drive the exogenous gene expression.19 Approaches to develop a replication-selective oncolytic adenovirus by replacing the promoters of essential genes with the hTERT promoter, were well-documented.20–23 We thus proceeded to select the hTERT promoter for regulating the expression of viral essential gene that further optimized the safety of the virus.
Reverse engineering approach: a step towards a new era of vaccinology with special reference to Salmonella
Published in Expert Review of Vaccines, 2022
Shania Vij, Reena Thakur, Praveen Rishi
Various online tools such as the NCBI Genome database, the Swiss-Prot protein database, Database of essential genes (DEG), Kyoto Encyclopedia of Genes and Genomes (KEGG), BLAST tools (http://blast.ncbi.nlm.nih.gov/Blast.cgi), Virulence factor database (VFDB), and cellular localization prediction tools, such as CELLO, PSLpred, and PSORTb form an integral component of subtractive genomics-based strategy to identify bacterial targets. Briefly, after collecting the genomes and proteomes of host and target pathogen from NCBI, BLAST is performed to subtract the non-host homologous genes of bacteria. Identified non-homologous gene and protein is subjected to BLASTx and BLASTp, using DEG server. BLAST hit with significant cutoff values against any bacterial sequence available in DEG indicates that the query sequence is a putative essential gene. These are then mapped for pathogen-specific metabolic pathways using KEGG server. Essential non-host homologues which are vital in these metabolic pathways are identified and analyzed to determine their subcellular location.
Identification of adverse drug reactions that may be related to pharmacogenetics in a public hospital in the South of Brazil
Published in Expert Opinion on Drug Safety, 2023
Amanda C. Camargo, Ursula Matte, Mariana R. Botton
Additionally, CYP2C19 could influence the response of 7 drugs that were associated with 17 ADRs. CYP2C19 is also a critical enzyme since it is responsible for the metabolism of 3% of the commonly used drugs [30]. Based on the allele frequencies in Southern Brazil [31], 27.0%, 24.8%, 4.4%, and 2.1% of individuals are Rapid, Intermediate, Ultrarapid, and Poor metabolizers for CYP2C19. Therefore, a significant part of individuals (58.3%) can present a response outside the therapeutic range using drugs metabolized by this enzyme. Another essential gene was CYP2C9, which can influence the effect of six drugs that were related to 16 ADRs. The estimated frequencies for Intermediate and Poor Metabolizers in the South of Brazil were 31.5% and 2.0%, respectively. So that 33.5% of individuals could present some ADR or lack of efficacy while using drugs metabolized by CYP2C9. Regarding HLA-B, the high-resolution data for Southern Brazil is sparse; however, according to CPIC, HLA-B*15:02 (allele related to the drugs approached in the study) shows a frequency of 0.006% in Europeans and 0.1% in African-Americans and Afro-Caribbeans [32].
Related Knowledge Centers
- DNA Replication
- Open Reading Frame
- Protein
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- Transposable Element
- Metabolism
- Gene
- Translation
- Natural Selection
- Fitness