scholarly journals nsd, a Locus That Affects the Myxococcus xanthus Cellular Response to Nutrient Concentration

2004 ◽  
Vol 186 (11) ◽  
pp. 3461-3471 ◽  
Author(s):  
Margaret Brenner ◽  
Anthony G. Garza ◽  
Mitchell Singer

ABSTRACT Expression of the previously reported Tn5lac Ω4469 insertion in Myxococcus xanthus cells is regulated by the starvation response. Interested in learning more about the starvation response, we cloned and sequenced the region containing the insertion. Our analysis shows that the gene fusion is located in an open reading frame that we have designated nsd (nutrient sensing/utilizing defective) and that its expression is driven by a σ70-like promoter. Sequence analysis of the nsd gene product provides no information on the potential structure or function of the encoded protein. In a further effort to learn about the role of nsd in the starvation response, we closely examined the phenotype of cells carrying the nsd::Tn5lac Ω4469 mutation. Our analysis showed that these cells initiate development on medium that contains nutrients sufficient to sustain vegetative growth of wild-type cells. Furthermore, in liquid media these same nutrient concentrations elicit a severe impairment of growth of nsd cells. The data suggest that the nsd cells launch a starvation response when there are enough nutrients to prevent one. In support of this hypothesis, we found that, when grown in these nutrient concentrations, nsd cells accumulate guanosine tetraphosphate, the cellular starvation signal. Therefore, we propose that nsd is used by cells to respond to available nutrient levels.

2005 ◽  
Vol 79 (23) ◽  
pp. 14719-14729 ◽  
Author(s):  
Wolfgang Resch ◽  
Bernard Moss

ABSTRACT We provide the initial characterization of the product of the vaccinia virus L3L open reading frame (VACWR090), which is conserved in all sequenced members of the poxvirus family. The predicted polypeptide contains no motifs or other features that provided a clue to the role of the L3 protein, and no functional information was available regarding a homolog discovered in Plasmodium falciparum. The L3 protein was expressed following viral DNA replication, a finding consistent with a putative late promoter sequence, and was packaged as a non-membrane protein in mature virus particles. A recombinant virus, in which the L3L gene was regulated by the Escherichia coli lac operator/repressor system, had a conditional lethal phenotype. The virus replicated in the presence of inducer, but in its absence, the yields of infectious virus were reduced by 99%. When cells were infected without inducer, however, no defect in gene expression or morphogenesis was noted. Virus particles lacking L3, which assembled in the absence of inducer, were indistinguishable from wild-type virions with regard to morphology, major structural proteins, and DNA content but were noninfectious. L3-deficient virions were able to bind and penetrate cells but produced extremely small amounts of viral early mRNA. A defect in transcription was demonstrated by in vitro studies with permeabilized virions, but soluble extracts of L3-deficient virions showed normal levels of template-dependent transcriptional activity, indicating that only transcription of the packaged genome is impaired.


2020 ◽  
Vol 63 (2) ◽  
pp. 46-62
Author(s):  
Suren T. Zolyan

We discuss the role of linguistic metaphors as a cognitive frame for the understanding of genetic information processing. The essential similarity between language and genetic information processing has been recognized since the very beginning, and many prominent scholars have noted the possibility of considering genes and genomes as texts or languages. Most of the core terms in molecular biology are based on linguistic metaphors. The processing of genetic information is understood as some operations on text – writing, reading and editing and their specification (encoding/decoding, proofreading, transcription, translation, reading frame). The concept of gene reading can be traced from the archaic idea of the equation of Life and Nature with the Book. Thus, the genetics itself can be metaphorically represented as some operations on text (deciphering, understanding, code-breaking, transcribing, editing, etc.), which are performed by scientists. At the same time linguistic metaphors portrayed gene entities also as having the ability of reading. In the case of such “bio-reading” some essential features similar to the processes of human reading can be revealed: this is an ability to identify the biochemical sequences based on their function in an abstract system and distinguish between type and its contextual tokens of the same type. Metaphors seem to be an effective instrument for representation, as they make possible a two-dimensional description: biochemical by its experimental empirical results and textual based on the cognitive models of comprehension. In addition to their heuristic value, linguistic metaphors are based on the essential characteristics of genetic information derived from its dual nature: biochemical by its substance, textual (or quasi-textual) by its formal organization. It can be concluded that linguistic metaphors denoting biochemical objects and processes seem to be a method of description and explanation of these heterogeneous properties.


Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1184
Author(s):  
Jean-Marc Zingg ◽  
Adelina Vlad ◽  
Roberta Ricciarelli

Levels of oxidized low-density lipoproteins (oxLDLs) are usually low in vivo but can increase whenever the balance between formation and scavenging of free radicals is impaired. Under normal conditions, uptake and degradation represent the physiological cellular response to oxLDL exposure. The uptake of oxLDLs is mediated by cell surface scavenger receptors that may also act as signaling molecules. Under conditions of atherosclerosis, monocytes/macrophages and vascular smooth muscle cells highly exposed to oxLDLs tend to convert to foam cells due to the intracellular accumulation of lipids. Moreover, the atherogenic process is accelerated by the increased expression of the scavenger receptors CD36, SR-BI, LOX-1, and SRA in response to high levels of oxLDL and oxidized lipids. In some respects, the effects of oxLDLs, involving cell proliferation, inflammation, apoptosis, adhesion, migration, senescence, and gene expression, can be seen as an adaptive response to the rise of free radicals in the vascular system. Unlike highly reactive radicals, circulating oxLDLs may signal to cells at more distant sites and possibly trigger a systemic antioxidant defense, thus elevating the role of oxLDLs to that of signaling molecules with physiological relevance.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1334
Author(s):  
Ye Liu ◽  
Zahra Mohri ◽  
Wissal Alsheikh ◽  
Umber Cheema

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Wasim Feroz ◽  
Arwah Mohammad Ali Sheikh

Abstract Background Cells have evolved balanced mechanisms to protect themselves by initiating a specific response to a variety of stress. The TP53 gene, encoding P53 protein, is one of the many widely studied genes in human cells owing to its multifaceted functions and complex dynamics. The tumour-suppressing activity of P53 plays a principal role in the cellular response to stress. The majority of the human cancer cells exhibit the inactivation of the P53 pathway. In this review, we discuss the recent advancements in P53 research with particular focus on the role of P53 in DNA damage responses, apoptosis, autophagy, and cellular metabolism. We also discussed important P53-reactivation strategies that can play a crucial role in cancer therapy and the role of P53 in various diseases. Main body We used electronic databases like PubMed and Google Scholar for literature search. In response to a variety of cellular stress such as genotoxic stress, ischemic stress, oncogenic expression, P53 acts as a sensor, and suppresses tumour development by promoting cell death or permanent inhibition of cell proliferation. It controls several genes that play a role in the arrest of the cell cycle, cellular senescence, DNA repair system, and apoptosis. P53 plays a crucial role in supporting DNA repair by arresting the cell cycle to purchase time for the repair system to restore genome stability. Apoptosis is essential for maintaining tissue homeostasis and tumour suppression. P53 can induce apoptosis in a genetically unstable cell by interacting with many pro-apoptotic and anti-apoptotic factors. Furthermore, P53 can activate autophagy, which also plays a role in tumour suppression. P53 also regulates many metabolic pathways of glucose, lipid, and amino acid metabolism. Thus under mild metabolic stress, P53 contributes to the cell’s ability to adapt to and survive the stress. Conclusion These multiple levels of regulation enable P53 to perform diversified roles in many cell responses. Understanding the complete function of P53 is still a work in progress because of the inherent complexity involved in between P53 and its target proteins. Further research is required to unravel the mystery of this Guardian of the genome “TP53”.


2009 ◽  
Vol 187 (7) ◽  
pp. 1101-1116 ◽  
Author(s):  
Chiara Francavilla ◽  
Paola Cattaneo ◽  
Vladimir Berezin ◽  
Elisabeth Bock ◽  
Diletta Ami ◽  
...  

Neural cell adhesion molecule (NCAM) associates with fibroblast growth factor (FGF) receptor-1 (FGFR1). However, the biological significance of this interaction remains largely elusive. In this study, we show that NCAM induces a specific, FGFR1-mediated cellular response that is remarkably different from that elicited by FGF-2. In contrast to FGF-induced degradation of endocytic FGFR1, NCAM promotes the stabilization of the receptor, which is recycled to the cell surface in a Rab11- and Src-dependent manner. In turn, FGFR1 recycling is required for NCAM-induced sustained activation of various effectors. Furthermore, NCAM, but not FGF-2, promotes cell migration, and this response depends on FGFR1 recycling and sustained Src activation. Our results implicate NCAM as a nonconventional ligand for FGFR1 that exerts a peculiar control on the intracellular trafficking of the receptor, resulting in a specific cellular response. Besides introducing a further level of complexity in the regulation of FGFR1 function, our findings highlight the link of FGFR recycling with sustained signaling and cell migration and the critical role of these events in dictating the cellular response evoked by receptor activation.


1998 ◽  
Vol 10 (6) ◽  
pp. 552-559 ◽  
Author(s):  
W. David Jarvis ◽  
Steven Grant

1988 ◽  
Vol 8 (9) ◽  
pp. 3898-3905 ◽  
Author(s):  
C Huxley ◽  
T Williams ◽  
M Fried

The mouse surfeit locus is unusual in that it contains a number of closely clustered genes (Surf-1, -2, and -4) that alternate in their direction of transcription (T. Williams, J. Yon, C. Huxley, and M. Fried, Proc. Natl. Acad. Sci. USA 85:3527-3530, 1988). The heterogeneous 5' ends of Surf-1 and Surf-2 are separated by 15 to 73 base pairs (bp), and the 3' ends of Surf-2 and Surf-4 overlap by 133 bp (T. Williams and M. Fried, Mol. Cell. Biol. 6:4558-4569, 1986; T. Williams and M. Fried, Nature (London) 322:275-279, 1986). A fourth gene in this locus, Surf-3, which is a member of a multigene family, has been identified. The poly(A) addition site of Surf-3 lies only 70 bp from the poly(A) addition site of Surf-1. Transcription of Surf-3 has been studied in the absence of the other members of its multigene family after transfection of a cloned genomic mouse DNA fragment, containing the Surf-3 gene, into heterologous monkey cells. Surf-3 specifies a highly expressed 1.0-kilobase mRNA that contains a long open reading frame of 266 amino acids, which would encode a highly basic polypeptide (23% Arg plus Lys). The other members of the Surf-3 multigene family are predominantly, if not entirely, intronless pseudogenes with the hallmarks of being generated by reverse transcription. The role of the very tight clustering on regulation of expression of the genes in the surfeit locus is discussed.


Development ◽  
2021 ◽  
Vol 148 (24) ◽  
Author(s):  
Samantha A. Russell ◽  
Kaitlin M. Laws ◽  
Greg J. Bashaw

ABSTRACT The Netrin receptor Frazzled/Dcc (Fra in Drosophila) functions in diverse tissue contexts to regulate cell migration, axon guidance and cell survival. Fra signals in response to Netrin to regulate the cytoskeleton and also acts independently of Netrin to directly regulate transcription during axon guidance in Drosophila. In other contexts, Dcc acts as a tumor suppressor by directly promoting apoptosis. In this study, we report that Fra is required in the Drosophila female germline for the progression of egg chambers through mid-oogenesis. Loss of Fra in the germline, but not the somatic cells of the ovary, results in the degeneration of egg chambers. Although a failure in nutrient sensing and disruptions in egg chamber polarity can result in degeneration at mid-oogenesis, these factors do not appear to be affected in fra germline mutants. However, similar to the degeneration that occurs in those contexts, the cell death effector Dcp-1 is activated in fra germline mutants. The function of Fra in the female germline is independent of Netrin and requires the transcriptional activation domain of Fra. In contrast to the role of Dcc in promoting cell death, our observations reveal a role for Fra in regulating germline survival by inhibiting apoptosis.


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