The ubiquitin ligase activity of the anaphase-promoting complex (APC)/cyclosome needs to be tightly regulated for proper cell cycle progression. Substrates are recruited to the APC by the Cdc20 and Cdh1 accessory proteins. The Cdh1-APC interaction is inhibited through phosphorylation of Cdh1 by Cdc28, the major cyclin-dependent protein kinase in budding yeast. More recently, Acm1 was reported to be a Cdh1-binding and -inhibitory protein in budding yeast. We found that although Acm1 is an unstable protein and contains the KEN-box and D-box motifs typically found in APC substrates, Acm1 itself is not an APC substrate. Rather, it uses these motifs to compete with substrates for Cdh1 binding, thereby inhibiting their recruitment to the APC. Mutation of these motifs prevented Acm1-Cdh1 binding in vivo and rendered Acm1 inactive both in vitro and in vivo. Acm1 stability was critically dependent on phosphorylation by Cdc28, as Acm1 was destabilized following inhibition of Cdc28, mutation of consensus Cdc28 phosphorylation sites in Acm1, or deletion of the Bmh1 and Bmh2 phosphoprotein-binding proteins. Thus, Cdc28 serves dual roles in inhibiting Cdh1-dependent APC activity during the cell cycle: stabilization of the Cdh1 inhibitor Acm1 and direct phosphorylation of Cdh1 to prevent its association with the APC.
- American Society for Microbiology
- Pseudosubstrate inhibition of the anaphase-promoting complex by ...
New California Regulations Pose Challenges and Potential Economic Benefits for Industrial Facilities
States like California are well on their way to implementing laws, rules, and regulations that call for more community ambient air quality monitoring and greater transparency from the chemical industry. For instance, California Assembly Bill 617, signed into law this July, establishes a statewide air monitoring network and calls for greater community air quality monitoring in and around chemical facilities. At the same time Assembly Bill 1647, signed into law earlier this month, directs local air pollution...
Hurricanes Harvey and Irma highlight need for regulating developments
There’s a lingering image of the American Frontier where a calm breeze blows through endless prairies of tall grass, and “the skies are not cloudy all day.”As the prairies become more populated, they get paved over to make way for roads and westward expansion.The tall grass that once ran 14 feet deep is replaced with impermeable asphalt, and the calm quiet is replaced with bustling cities.On days where the blue skies are replaced with rain, the water has nowhere to go but over the impenetrable...
EC Publishes NanoData Landscape Compilation Reports
On June 8, 2017, the European Commission (EC) published eight NanoData Landscape Compilation reports. The EC states that the reports offer a snapshot of the environment for nanotechnology in different application fields: NanoData Landscape Compilation: Health: This report offers a snapshot of the status of the environment for nanotechnology in the context of health. Analysis of that environment, trends in the data, and the effects of European policies and actions on health nanotechnology will be reported in...
New York Legionella regulations: are they missing the boat?
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Report documents effects of 40 years of groundwater withdrawal
The cumulative effects of 40 years of groundwater withdrawals in the Houston-Galveston region are documented in a report from the United States Geological Survey. Decades of extensive withdrawals have caused the land to sink, or subside.The Houston-Galveston region is one of the largest areas of land surface subsidence in the U.S., according to the agency. Water withdrawals started as early as 1836, but routine, precise data gathering in the region began in the 1970s. The information has been used to inform water...