In G0 and early G1, complexes containing p130 (RBL2) and p107 (RBL1), respectively, and histone deacetylase HDAC1 bind the promoter of the CCNA2 gene (Rayman et al. 2002).
In G0 and early G1, complexes containing p130 (RBL2) and p107 (RBL1), respectively, and histone deacetylase HDAC1 bind the promoter of the CCNA2 gene (Rayman et al. 2002).
USP37 deubiquitinates Lys-11-linked polyubiquitin chains from cyclin-A (CCNA1 and CCNA2), which opposes the Lys-11-linked polyubiquitination mediated by the anaphase-promoting complex (APC/C) during G1/S transition, thereby promoting S phase entry. Phosphorylation by CDK2 at Ser-628 during G1/S phase maximizes USP37 deubiquitinase activity (Huang et al. 2011).
HuR (ELAVL1) is a ubiquitous protein that binds AU-rich elements in mRNAs and acts to stabilize the mRNAs. HuR activity is controlled by phosphorylation, with PKC alpha and PCK delta enhancing the ability of HuR to bind and stabilize mRNAs. Binding of mRNAs occurs in the nucleus and HuR then interacts with the CRM1 export pathway to transfer the mRNA to the cytoplasm. The mechanism by which HuR shields the mRNA from degradation is unknown. HuR also regulates translation of some mRNAs, in some cases repressing translation and in some cases enhancing translation of bound mRNAs by recruiting them to polysomes. HuR binds and regulates mRNAs encoding Cyclooxygenase-2 (COX2, PTGS2), Cyclin A (CCNA, CCNA2), Cyclin D1 (CCND1), Cyclin B1 (CCNB1), CD83 antigen (CD83), and proto-oncogene c-Fos (FOS). HuR is a member of a family of proteins that also contains HuD (ELAVL4), HuB (ELAVL2), and HuC (ELAVL3). HuB, HuC, and HuD are specifically expressed in neural tissue. HuR participates in apoptosis. During lethal stress HuR becomes mostly cytoplasmic and is a target of Caspase-3 and Caspase-7. The cleavage products of HuR in turn promote apoptosis.
Phosphorylated HuR (phosphoserine221 and phosphoserine318) binds AU-rich elements in the following mRNAs: Cyclooxygenase-2 (COX-2, PTGS2), Cyclin A (CCNA, CCNA2), and Cyclin D1 (CCND1).
Phosphorylated HuR (phosphoserine221 and phosphoserine318) binds AU-rich elements in the following mRNAs: Cyclooxygenase-2 (COX-2, PTGS2), Cyclin A (CCNA, CCNA2), and Cyclin D1 (CCND1).