scholarly journals Human Non-Hodgkin's Lymphomas Overexpress a Wild-Type Form of p53 Which Is a Functional Transcriptional Activator of the Cyclin-Dependent Kinase Inhibitor p21

Blood ◽  
1997 ◽  
Vol 89 (7) ◽  
pp. 2523-2528 ◽  
Author(s):  
Roberta Maestro ◽  
Annunziata Gloghini ◽  
Claudio Doglioni ◽  
Sara Piccinin ◽  
Tamara Vukosavljevic ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
P53 Protein ◽  
Growth Arrest ◽  
Protein Accumulation ◽  
Cyclin Dependent Kinase ◽  
Wild Type ◽  
Type Form ◽  
G1 Checkpoint ◽  
Hodgkin's Lymphomas ◽  
Wild Type Form

Abstract A large fraction of non-Hodgkin's lymphomas (NHLs) accumulate a wild-type form of the p53 tumor suppressor protein at the nuclear level. In normal cells, p53 induction is associated with a temporary cell growth arrest at the G1-S boundary of the cell cycle. This activity of p53 as a G1 checkpoint molecule is strictly dependent on its ability to induce the transcription of the inhibitor of the cyclin dependent kinase, p21. To verify the functionality of the wild-type p53 protein accumulated in NHL cells, 70 cases were comparatively analyzed for p53 and p21 expression and status of the respective genes. Overexpression of the wt p53 protein was associated with the accumulation of p21, indicating that p53 is functional with respect to p21 induction in these tumors. The coaccumulation of p53 with Ki-67 antigen indicates that wt p53-positive cells and p21-positive cells, as well, are actively proliferative elements, supporting the notion that p53-induced, p21-mediated growth arrest is somehow overridden in NHL cells. No p21 mutation or particular allele variant was shown to correlate with p21 protein accumulation, thus excluding a role for p21 structural abnormalities. Taken together, our data suggest the existence in NHL of a peculiar mechanism of functional inactivation of the p53 G1 checkpoint pathway occurring downstream of the CDK inhibitor p21.

scholarly journals Gain-of-Function Mutant p53: All the Roads Lead to Tumorigenesis

2019 ◽  
Vol 20 (24) ◽  
pp. 6197 ◽  
Author(s):  
Yan Stein ◽  
Varda Rotter ◽  
Ronit Aloni-Grinstein
Keyword(s):  
Protein Interactions ◽  
Therapeutic Strategy ◽  
P53 Protein ◽  
Mutant P53 ◽  
Wild Type ◽  
Protein Protein Interactions ◽  
Gain Of Function ◽  
Central Node ◽  
Type Form ◽  
Wild Type Form

The p53 protein is mutated in about 50% of human cancers. Aside from losing the tumor-suppressive functions of the wild-type form, mutant p53 proteins often acquire inherent, novel oncogenic functions, a phenomenon termed mutant p53 gain-of-function (GOF). A growing body of evidence suggests that these pro-oncogenic functions of mutant p53 proteins are mediated by affecting the transcription of various genes, as well as by protein–protein interactions with transcription factors and other effectors. In the current review, we discuss the various GOF effects of mutant p53, and how it may serve as a central node in a network of genes and proteins, which, altogether, promote the tumorigenic process. Finally, we discuss mechanisms by which “Mother Nature” tries to abrogate the pro-oncogenic functions of mutant p53. Thus, we suggest that targeting mutant p53, via its reactivation to the wild-type form, may serve as a promising therapeutic strategy for many cancers that harbor mutant p53. Not only will this strategy abrogate mutant p53 GOF, but it will also restore WT p53 tumor-suppressive functions.

scholarly journals Synergism of imipenem with fosfomycin associated with the active cell wall recycling and heteroresistance in Acinetobacter calcoaceticus-baumannii complex

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Uthaibhorn Singkham-in ◽  
Tanittha Chatsuwan
Keyword(s):  
Cell Wall ◽  
De Novo ◽  
Acinetobacter Calcoaceticus ◽  
Active Cell ◽  
Wild Type ◽  
Cell Wall Metabolism ◽  
Carbapenem Resistant ◽  
Type Form ◽  
Wild Type Form ◽  
Cell Wall Recycling

AbstractThe carbapenem-resistant Acinetobacter calcoaceticus-baumannii (ACB) complex has become an urgent threat worldwide. Here, we determined antibiotic combinations and the feasible synergistic mechanisms against three couples of ACB (A. baumannii (AB250 and A10), A. pittii (AP1 and AP23), and A. nosocomialis (AN4 and AN12)). Imipenem with fosfomycin, the most effective in the time-killing assay, exhibited synergism to all strains except AB250. MurA, a fosfomycin target encoding the first enzyme in the de novo cell wall synthesis, was observed with the wild-type form in all isolates. Fosfomycin did not upregulate murA, indicating the MurA-independent pathway (cell wall recycling) presenting in all strains. Fosfomycin more upregulated the recycling route in synergistic strain (A10) than non-synergistic strain (AB250). Imipenem in the combination dramatically downregulated the recycling route in A10 but not in AB250, demonstrating the additional effect of imipenem on the recycling route, possibly resulting in synergism by the agitation of cell wall metabolism. Moreover, heteroresistance to imipenem was observed in only AB250. Our results indicate that unexpected activity of imipenem on the active cell wall recycling concurrently with the presence of heteroresistance subpopulation to imipenem may lead to the synergism of imipenem and fosfomycin against the ACB isolates.

p21WAF1 Control of Epithelial Cell Cycle and Cell Fate

2002 ◽  
Vol 13 (6) ◽  
pp. 453-464 ◽  
Author(s):  
Wendy C. Weinberg ◽  
Mitchell F. Denning
Keyword(s):  
Cell Cycle ◽  
Epithelial Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Kinase Inhibitor ◽  
Growth Arrest ◽  
Nuclear Antigen ◽  
Central Position ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor

As a broad-acting cyclin-dependent kinase inhibitor, p21WAF1 occupies a central position in the cell cycle regulation of self-renewing tissues such as oral mucosa and skin. In addition to regulating normal cell cycle progression decisions, p21WAF1 integrates genotoxic insults into growth arrest and apoptotic signaling pathways that ultimately determine cell fate. As a result of its complex interactions with cell cycle machinery and response to mutagenic agents, p21WAF1 also has stage-specific roles in epithelial carcinogenesis. Finally, a view is emerging of p21WAF1 as not merely a cyclin-dependent kinase inhibitor, but also as a direct participant in regulating genes involved in growth arrest, senescence, and aging, thus providing an additional layer of control over matters of the cell cycle. This review discusses these various roles played by p21WAF1 in cell cycle control, and attempts to relate these to epithelial cell biology, with special emphasis on keratinocytes. (Abbreviations used include the following: Brdu, 5-Bromo-2-deoxyuridine; cdk, cyclin-dependent kinase; EGF, epidermal growth factor; KIP, kinase inhibitor protein; PCNA, proliferating cell nuclear antigen; and TPA, 12-O-tetradecanoylphorbol-13-acetate.)

scholarly journals Inactivation of the selB Gene in Methanococcus maripaludis: Effect on Synthesis of Selenoproteins and Their Sulfur-Containing Homologs

2003 ◽  
Vol 185 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Michael Rother ◽  
Isabella Mathes ◽  
Friedrich Lottspeich ◽  
August Böck
Keyword(s):  
Gene Product ◽  
Formate Dehydrogenase ◽  
Selenium Supplementation ◽  
Wild Type ◽  
Methanococcus Maripaludis ◽  
Translation Factor ◽  
Type Form ◽  
And Function ◽  
Sulfur Containing ◽  
Wild Type Form

ABSTRACT The genome of Methanococcus maripaludis harbors genes for at least six selenocysteine-containing proteins and also for homologs that contain a cysteine codon in the position of the UGA selenocysteine codon. To investigate the synthesis and function of both the Se and the S forms, a mutant with an inactivated selB gene was constructed and analyzed. The mutant was unable to synthesize any of the selenoproteins, thus proving that the gene product is the archaeal translation factor (aSelB) specialized for selenocysteine insertion. The wild-type form of M. maripaludis repressed the synthesis of the S forms of selenoproteins, i.e., the selenium-independent alternative system, in selenium-enriched medium, but the mutant did not. We concluded that free selenium is not involved in regulation but rather a successional compound such as selenocysteyl-tRNA or some selenoprotein. Apart from the S forms, several enzymes from the general methanogenic route were affected by selenium supplementation of the wild type or by the selB mutation. Although the growth of M. maripaludis on H2/CO2 is only marginally affected by the selB lesion, the gene is indispensable for growth on formate because M. maripaludis possesses only a selenocysteine-containing formate dehydrogenase.

Activin induces hepatocyte cell growth arrest through induction of the cyclin-dependent kinase inhibitor p15INK4B and Sp1

2004 ◽  
Vol 16 (6) ◽  
pp. 693-701 ◽  
Author(s):  
Joanne Ho ◽  
Chantal de Guise ◽  
Christie Kim ◽  
Serge Lemay ◽  
Xiao-Fan Wang ◽  
...  
Keyword(s):  
Cell Growth ◽  
Kinase Inhibitor ◽  
Growth Arrest ◽  
Cyclin Dependent Kinase ◽  
Cell Growth Arrest ◽  
Cyclin Dependent Kinase Inhibitor

scholarly journals Seed Production and Germination of Eight Cultivars and the Wild Type of Ruellia tweediana: A Potentially Invasive Ornamental

2003 ◽  
Vol 21 (3) ◽  
pp. 137-143 ◽  
Author(s):  
Sandra B. Wilson ◽  
Laurie K. Mecca
Keyword(s):  
Seed Production ◽  
Invasive Plant ◽  
Temperature Treatment ◽  
Native Plant ◽  
Wild Type ◽  
Type Form ◽  
Storage Studies ◽  
Exotic Pest ◽  
Exotic Pest Plant ◽  
Wild Type Form

Abstract Seed production and the influence of light and temperature on germination were determined for eight cultivars and the wild type form of Mexican petunia (Ruellia tweediana Griseb). The wild type form of R. tweediana has been ranked by the Florida Exotic Pest Plant Council as a Category I invasive plant, meaning it has invaded and is disrupting native plant communities in Florida. The cultivar ‘Purple Showers’ did not set any seed. Peak flowering and seed production for other cultivars generally occurred in August with ‘Morado Chi’, ‘Chi Chi’, and the wild type plants producing approximately three times the amount of seed produced by ‘Katie Pink’, ‘Katie Purple’, ‘Katie White’, and ‘Snow White’. For seed germination, significant cultivar x light interactions occurred for each temperature treatment. Some germination was observed at each temperature except for ‘Katie Purple’, ‘Katie Variegated’, and ‘Katie White’ at 33C (91.4F) without light. Regardless of cultivar or provision of light, 94-100% germination occurred at 30/20C (86/68F), with the exception of ‘Katie Purple’ (65%), ‘Katie Variegated’ (54%), and ‘Katie White’ (83%) without light. At 15, 24 or 33C (59, 75.2, and 91.4F), germination was generally greatest for ‘Chi Chi’ (with or without light) and ‘Morado Chi’ (with light). In parallel greenhouse studies, where seeds were germinated in pots containing a soilless medium, highest germination was achieved by ‘Chi Chi’, ‘Katie Pink’, ‘Katie Variegated’ and ‘Morado Chi’, while significantly lower germination was achieved by wild type plants (55%) by day 14. Storage studies demonstrated that germination of seed collected from the wild type and ‘Chi Chi’ plants began to decrease between 6 and 12 months when maintained at 24C (75.2F) but had equal (‘Chi Chi’) or higher (wild type) germination when maintained at 4C (39.2F) for 12 months.

scholarly journals Growth arrest by the cyclin-dependent kinase inhibitor p27Kip1 is abrogated by c-Myc.

1996 ◽  
Vol 15 (23) ◽  
pp. 6595-6604 ◽  
Author(s):  
J. Vlach ◽  
S. Hennecke ◽  
K. Alevizopoulos ◽  
D. Conti ◽  
B. Amati
Keyword(s):  
Kinase Inhibitor ◽  
Growth Arrest ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor

scholarly journals Biofilm-Constructing Variants of Paraburkholderia phytofirmans PsJN Outcompete the Wild-Type Form in Free-Living and Static Conditions but Not In Planta

2019 ◽  
Vol 85 (11) ◽  
Author(s):  
Marine Rondeau ◽  
Qassim Esmaeel ◽  
Jérôme Crouzet ◽  
Pauline Blin ◽  
Isabelle Gosselin ◽  
...  
Keyword(s):  
Wild Type ◽  
In Planta ◽  
Free Living ◽  
Iron Sulfur Cluster ◽  
Content Type ◽  
Iron Sulfur ◽  
Type Form ◽  
Static Conditions ◽  
Wild Type Form

ABSTRACT Members of the genus Burkholderia colonize diverse ecological niches. Among the plant-associated strains, Paraburkholderia phytofirmans PsJN is an endophyte with a broad host range. In a spatially structured environment (unshaken broth cultures), biofilm-constructing specialists of P. phytofirmans PsJN colonizing the air-liquid interface arose at high frequency. In addition to forming a robust biofilm in vitro and in planta on Arabidopsis roots, those mucoid phenotypic variants display a reduced swimming ability and modulate the expression of several microbe-associated molecular patterns (MAMPs), including exopolysaccharides (EPS), flagellin, and GroEL. Interestingly, the variants induce low PR1 and PDF1.2 expression compared to that of the parental strain, suggesting a possible evasion of plant host immunity. We further demonstrated that switching from the planktonic to the sessile form did not involve quorum-sensing genes but arose from spontaneous mutations in two genes belonging to an iron-sulfur cluster: hscA (encoding a cochaperone protein) and iscS (encoding a cysteine desulfurase). A mutational approach validated the implication of these two genes in the appearance of variants. We showed for the first time that in a heterogeneous environment, P. phytofirmans strain PsJN is able to rapidly diversify and coexpress a variant that outcompete the wild-type form in free-living and static conditions but not in planta. IMPORTANCE Paraburkholderia phytofirmans strain PsJN is a well-studied plant-associated bacterium known to induce resistance against biotic and abiotic stresses. In this work, we described the spontaneous appearance of mucoid variants in PsJN from static cultures. We showed that the conversion from the wild-type (WT) form to variants (V) correlates with an overproduction of EPS, an enhanced ability to form biofilm in vitro and in planta, and a reduced swimming motility. Our results revealed also that these phenotypes are in part associated with spontaneous mutations in an iron-sulfur cluster. Overall, the data provided here allow a better understanding of the adaptive mechanisms likely developed by P. phytofirmans PsJN in a heterogeneous environment.

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