The second subunit of the replication factor C complex (RFC40) and the regulatory subunit (RIalpha) of protein kinase A form a protein complex promoting cell survival
Autor: | Rakhee S, Gupte, Yun, Weng, Li, Liu, Marietta Y W T, Lee |
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Rok vydání: | 2005 |
Předmět: |
Cell Survival
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit Immunoblotting 8-Bromo Cyclic Adenosine Monophosphate Down-Regulation Cyclic AMP-Dependent Protein Kinases Cell Line Gene Expression Regulation Neoplastic Cell Line Tumor Multiprotein Complexes Two-Hybrid System Techniques Protein Interaction Mapping Humans Immunoprecipitation Replication Protein C |
Zdroj: | Cell cycle (Georgetown, Tex.). 4(2) |
ISSN: | 1551-4005 |
Popis: | Replication Factor C (RFC) is required for the loading of Proliferating Cell Nuclear Antigen (PCNA) onto DNA during DNA replication, repair and recombination. RFC40, the second subunit of the RFC complex, and PCNA have been shown to be overexpressed in gestational trophoblastic diseases. Using RFC40 as the bait in a yeast two-hybrid screening, we have identified a novel interaction between RFC40 and the regulatory subunit (RIalpha) of cAMP-dependent Protein kinase A (PKA). The interaction sites between these two proteins were investigated and mapped to the N-terminus of RIalpha and the C-terminus of RFC40. Moreover, it was demonstrated that the C-subunit of PKA was not associated with the RFC40-RIalpha complex. Furthermore, RFC37, the third subunit of the RFC complex, competes with RIalpha and displaces it from the RFC40-RIalpha complex. Interestingly, downregulation of endogenous RIalpha by 8-chloro cAMP, in MCF7 breast cancer cells led to reduction in the amount of RFC40-RIalpha complex, together with decrease in cell survival. |
Databáze: | OpenAIRE |
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