Cdc25B is a key regulator of entry into mitosis, and its activity and localization are regulated ... more Cdc25B is a key regulator of entry into mitosis, and its activity and localization are regulated by binding of the 14-3-3 dimer. There are three 14-3-3 binding sites on Cdc25B, with Ser 323 being the highest affinity binding and is highly homologous to the Ser 216 14-3-3 binding site on Cdc25C. Loss of 14-3-3 binding to Ser 323 increases cyclin/Cdk substrate access to the catalytic site, thereby increasing its activity. It also affects the localization of Cdc25B. Thus, phosphorylation and 14-3-3 binding to this site is essential for down-regulating Cdc25B activity, blocking its mitosis promoting function. The question of how this inhibitory signal is relieved to allow Cdc25B activation and entry into mitosis is yet to be resolved. Here, we show that Ser 323 phosphorylation is maintained into mitosis, but phosphorylation of Ser 321 disrupts 14-3-3 binding to Ser 323 , mimicking the effect of inhibiting Ser 323 phosphorylation on both Cdc25B activity and localization. The unphosphorylated Ser 321 appears to have a role in stabilizing 14-3-3 binding to Ser 323 , and loss of the Ser hydroxyl group appears to be sufficient to significantly reduce 14-3-3 binding. A consequence of loss of 14-3-3 binding is dephosphorylation of Ser 323. Ser 321 is phosphorylated in mitosis by Cdk1. The mitotic phosphorylation of Ser 321 acts to maintain full activation of Cdc25B by disrupting 14-3-3 binding to Ser 323 and enhancing the dephosphorylation of Ser 323 to block 14-3-3 binding to this site.
Background: The high incidence of microbial infection and the emergence of drug resistant and mul... more Background: The high incidence of microbial infection and the emergence of drug resistant and multidrugresistant microbes as well as the lack of any current chemotherapy augmented the necessity to search for new and better antimicrobial drug. Marine invertebrates are known as rich sources of compounds with unique chemical structures and pronounced chemical and biological activities, which suggests potential value as lead structures for the development of new pharmaceuticals. Objective: This study aims to screen potential antiinfective of sponges extracts collected from Barrang Lompo island and report on their antibacterial and antifungal properties. Methods: Testing for anti-infective agents was conducted using dilution method. Nutrient Agar was used as the testing media and nutrient broth for the inoculation of microorganisms. Staphylococcus aureus, Escherichia coil and Salmonella thypi were used as the testing bacteria and Candida albicans for the testing fungi. Chloramphenicol wa...
Cdc25B is a key regulator of entry into mitosis, and its activity and localization are regulated ... more Cdc25B is a key regulator of entry into mitosis, and its activity and localization are regulated by binding of the 14-3-3 dimer. There are three 14-3-3 binding sites on Cdc25B, with Ser 323 being the highest affinity binding and is highly homologous to the Ser 216 14-3-3 binding site on Cdc25C. Loss of 14-3-3 binding to Ser 323 increases cyclin/Cdk substrate access to the catalytic site, thereby increasing its activity. It also affects the localization of Cdc25B. Thus, phosphorylation and 14-3-3 binding to this site is essential for down-regulating Cdc25B activity, blocking its mitosis promoting function. The question of how this inhibitory signal is relieved to allow Cdc25B activation and entry into mitosis is yet to be resolved. Here, we show that Ser 323 phosphorylation is maintained into mitosis, but phosphorylation of Ser 321 disrupts 14-3-3 binding to Ser 323 , mimicking the effect of inhibiting Ser 323 phosphorylation on both Cdc25B activity and localization. The unphosphorylated Ser 321 appears to have a role in stabilizing 14-3-3 binding to Ser 323 , and loss of the Ser hydroxyl group appears to be sufficient to significantly reduce 14-3-3 binding. A consequence of loss of 14-3-3 binding is dephosphorylation of Ser 323. Ser 321 is phosphorylated in mitosis by Cdk1. The mitotic phosphorylation of Ser 321 acts to maintain full activation of Cdc25B by disrupting 14-3-3 binding to Ser 323 and enhancing the dephosphorylation of Ser 323 to block 14-3-3 binding to this site.
Background: The high incidence of microbial infection and the emergence of drug resistant and mul... more Background: The high incidence of microbial infection and the emergence of drug resistant and multidrugresistant microbes as well as the lack of any current chemotherapy augmented the necessity to search for new and better antimicrobial drug. Marine invertebrates are known as rich sources of compounds with unique chemical structures and pronounced chemical and biological activities, which suggests potential value as lead structures for the development of new pharmaceuticals. Objective: This study aims to screen potential antiinfective of sponges extracts collected from Barrang Lompo island and report on their antibacterial and antifungal properties. Methods: Testing for anti-infective agents was conducted using dilution method. Nutrient Agar was used as the testing media and nutrient broth for the inoculation of microorganisms. Staphylococcus aureus, Escherichia coil and Salmonella thypi were used as the testing bacteria and Candida albicans for the testing fungi. Chloramphenicol wa...
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