title: Replication factor C3 is a CREB target gene that regulates cell cycle progression through the modulation of chromatin loading of PCNA.
abstract: CREB (cyclic AMP response element-binding protein) is a transcription factor overexpressed in normal and neoplastic myelopoiesis and regulates cell cycle progression, although its oncogenic mechanism has not been well characterized. Replication factor C3 (RFC3) is required for chromatin loading of proliferating cell nuclear antigen (PCNA) which is a sliding clamp platform for recruiting numerous proteins in the DNA metabolism. CREB1 expression, which was activated by E2F, was coupled with RFC3 expression during the G1/S progression in the KG-1 acute myeloid leukemia (AML) cell line. There was also a direct correlation between the expression of RFC3 and CREB1 in human AML cell lines as well as in the AML cells from the patients. CREB interacted directly with the CRE site in RFC3 promoter region. CREB-knockdown inhibited primarily G1/S cell cycle transition by decreasing the expression of RFC3 as well as PCNA loading onto the chromatin. Exogenous expression of RFC3 was sufficient to rescue the impaired G1/S progression and PCNA chromatin loading caused by CREB knockdown. These studies suggest that RFC3 may have a role in neoplastic myelopoiesis by promoting the G1/S progression and its expression is regulated by CREB.
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: H-D
authors.initials: HD
authors.lastname: Chae
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Mitton
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Lacayo
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Sakamoto
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002843:Chromatin / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051818:Replication Protein C / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C115163:CREB1 protein, human; D002843:Chromatin; D017362:Cyclic AMP Response Element-Binding Protein; D018809:Proliferating Cell Nuclear Antigen; C497562:RFC3 protein, human; D012333:RNA, Messenger; D051818:Replication Protein C