ABSTRACT
Cyclin A accumulates at the onset of S phase, remains high during G(2) and early mitosis and is degraded at prometaphase. Here, we report that the acetyltransferase P/CAF directly interacts with cyclin A that as a consequence becomes acetylated at lysines 54, 68, 95 and 112. Maximal acetylation occurs simultaneously to ubiquitylation at mitosis, indicating importance of acetylation on cyclin A stability. This was further confirmed by the observation that the pseudoacetylated cyclin A mutant can be ubiquitylated whereas the nonacetylatable mutant cannot. The nonacetylatable mutant is more stable than cyclin A WT (cycA WT) and arrests cell cycle at mitosis. Moreover, in cells treated with histone deacetylase inhibitors cyclin A acetylation increases and its stability decreases, thus supporting the function of acetylation on cyclin A degradation. Although the nonacetylatable mutant cannot be ubiquitylated, it interacts with the proteins needed for its degradation (cdks, Cks, Cdc20, Cdh1 and APC/C). In fact, its association with cdks is increased and its complexes with these kinases display higher activity than control cycA WT-cdk complexes. All these results indicate that cyclin A acetylation at specific lysines is crucial for cyclin A stability and also has a function in the regulation of cycA-cdk activity.
Subject(s)
Cyclin A/metabolism , Cyclin-Dependent Kinase 2/metabolism , p300-CBP Transcription Factors/metabolism , Acetylation , Animals , COS Cells , Chlorocebus aethiops , Cyclin A/genetics , HeLa Cells , Humans , Lysine/genetics , Lysine/metabolism , MutationSubject(s)
Cavernous Sinus , Cutaneous Fistula/etiology , Ludwig's Angina/etiology , Osteomyelitis/etiology , Periapical Abscess/complications , Periodontal Abscess/complications , Sinus Thrombosis, Intracranial/etiology , Cutaneous Fistula/diagnosis , Diagnosis, Differential , Emergency Medicine , Humans , Ludwig's Angina/diagnosis , Osteomyelitis/diagnosis , Sinus Thrombosis, Intracranial/diagnosisABSTRACT
Direct sagittal computed tomography (CT) was performed in 454 patients thought to have internal derangement of the temporomandibular joint (TMJ). Of 905 joints examined, 71 were subsequently studied using arthrography and/or surgery. Sensitivity was 91.8%, accuracy 87.3%, and the positive predictive value 93.3%. Degenerative joint disease was detected in 33.6% of joints with anterior meniscal displacement but no reduction, 15.3% of those with displacement and reduction, and 5.0% of those with no identifiable meniscal abnormality. It is concluded that direct sagittal CT is a sensitive and effective method of detecting and characterizing displacement of the TMJ meniscus as well as underlying degenerative joint disease.
