title: Interaction of CR6 (GADD45gamma ) with proliferating cell nuclear antigen impedes negative growth control.
abstract: GADD45, MyD118, and CR6 (also termed GADD45alpha, beta, and gamma) comprise a family of genes that encode for related proteins playing important roles in negative growth control, including growth suppression. Data accumulated suggest that MyD118/GADD45/CR6 serve similar but not identical functions along different apoptotic and growth suppressive pathways. It is also apparent that individual members of the MyD118/GADD45/CR6 family are differentially induced by a variety of genetic and environmental stress agents. The MyD118, CR6, and GADD45 proteins were shown to predominantly localize within the cell nucleus. Recently, we have shown that both MyD118 and GADD45 interact with proliferating cell nuclear antigen (PCNA), a protein that plays a central role in DNA replication, DNA repair, and cell cycle progression, as well as with the universal cyclin-dependent kinase inhibitor p21. In this work we show that also CR6 interacts with PCNA and p21. Moreover, it is shown that CR6 interacts with PCNA via a domain that also mediates interaction of both GADD45 and MyD118 with PCNA. Importantly, evidence has been obtained that interaction of CR6 with PCNA impedes the function of this protein in negative growth control, similar to observations reported for MyD118 and GADD45.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology and the Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: N
authors.initials: N
authors.lastname: Azam
authors.forename: M
authors.initials: M
authors.lastname: Vairapandi
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Hoffman
authors.forename: D A
authors.initials: DA
authors.lastname: Liebermann
mesh_terms: D000943:Antigens, Differentiation; D017209:Apoptosis; D001665:Binding Sites; D002277:Carcinoma / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011485:Protein Binding; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D020798:Two-Hybrid System Techniques; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; C493956:CDKN1A protein, human; C086470:GADD45B protein, human; D000097642:GADD45 Proteins