scholarly journals In Silico Design of E3 Ubiquitin-Protein Ligase NEDD4-1 Inhibitors: An Alternative Approach for Targeting the MAPK Pathway in Cancer Therapy

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 10
Author(s):  
Pirolli ◽  
Righino ◽  
Tropea ◽  
Gurrieri ◽  
Sangiorgi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cancer Therapy ◽  
In Silico ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
In Silico Design ◽  
Ubiquitin Protein Ligase ◽  
Alternative Approach ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

Among all the several targets in common use in the antitumor therapies, the pharmacologicinhibition of the MAPK (Mitogen Activated Protein Kinase) pathway represents an efficienttherapeutic approach [1]. [...]

Regulation of spontaneous and induced resumption of meiosis in mouse oocytes by different intracellular pathways

Reproduction ◽  
2000 ◽  
pp. 377-383 ◽  
Author(s):  
L Leonardsen ◽  
A Wiersma ◽  
M Baltsen ◽  
AG Byskov ◽  
CY Andersen
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Mitogen Activated Protein Kinase ◽  
Meiotic Maturation ◽  
Mouse Oocytes ◽  
Mitogen Activated Protein ◽  
Dependent Signal ◽  
Kinase Pathway ◽  
Kinase A

The mitogen-activated protein kinase-dependent and the cAMP-protein kinase A-dependent signal transduction pathways were studied in cultured mouse oocytes during induced and spontaneous meiotic maturation. The role of the mitogen-activated protein kinase pathway was assessed using PD98059, which specifically inhibits mitogen-activated protein kinase 1 and 2 (that is, MEK1 and MEK2), which activates mitogen-activated protein kinase. The cAMP-dependent protein kinase was studied by treating oocytes with the protein kinase A inhibitor rp-cAMP. Inhibition of the mitogen-activated protein kinase pathway by PD98059 (25 micromol l(-1)) selectively inhibited the stimulatory effect on meiotic maturation by FSH and meiosis-activating sterol (that is, 4,4-dimethyl-5alpha-cholest-8,14, 24-triene-3beta-ol) in the presence of 4 mmol hypoxanthine l(-1), whereas spontaneous maturation in the absence of hypoxanthine was unaffected. This finding indicates that different signal transduction mechanisms are involved in induced and spontaneous maturation. The protein kinase A inhibitor rp-cAMP induced meiotic maturation in the presence of 4 mmol hypoxanthine l(-1), an effect that was additive to the maturation-promoting effect of FSH and meiosis-activating sterol, indicating that induced maturation also uses the cAMP-protein kinase A-dependent signal transduction pathway. In conclusion, induced and spontaneous maturation of mouse oocytes appear to use different signal transduction pathways.

scholarly journals cAMP abrogates the p21ras-mitogen-activated protein kinase pathway in fibroblasts.

1994 ◽  
Vol 269 (5) ◽  
pp. 3534-3538
Author(s):  
P.L. Hordijk ◽  
I. Verlaan ◽  
K. Jalink ◽  
E.J. van Corven ◽  
W.H. Moolenaar
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

scholarly journals Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jackson Peterson ◽  
Siqi Li ◽  
Erin Kaltenbrun ◽  
Ozgun Erdogan ◽  
Christopher M. Counter
Keyword(s):  
Amino Acids ◽  
Protein Kinase ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Rare Codons ◽  
Synonymous Codons ◽  
Multiple Components ◽  
Human Genes ◽  
Regulatory Module ◽  
Mitogen Activated Protein

AbstractThe ability to translate three nucleotide sequences, or codons, into amino acids to form proteins is conserved across all organisms. All but two amino acids have multiple codons, and the frequency that such synonymous codons occur in genomes ranges from rare to common. Transcripts enriched in rare codons are typically associated with poor translation, but in certain settings can be robustly expressed, suggestive of codon-dependent regulation. Given this, we screened a gain-of-function library for human genes that increase the expression of a GFPrare reporter encoded by rare codons. This screen identified multiple components of the mitogen activated protein kinase (MAPK) pathway enhancing GFPrare expression. This effect was reversed with inhibitors of this pathway and confirmed to be both codon-dependent and occur with ectopic transcripts naturally coded with rare codons. Finally, this effect was associated, at least in part, with enhanced translation. We thus identify a potential regulatory module that takes advantage of the redundancy in the genetic code to modulate protein expression.

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