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Transcriptional Control and Signal Transduction

Replication factor C3 is a CREB target gene that regulates cell cycle progression through the modulation of chromatin loading of PCNA

Leukemia volume 29, pages 1379–1389 (2015)Cite this article

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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.

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Acknowledgements

This research was supported by NIH R01 HL75826 (KMS), and by the American Cancer Society Greeley & Seattle Gala/Friends of Rob Kinas Postdoctoral Fellowship and the Stanford University Dean’s Post-Doctoral Fellowship program (BM). Sorting was performed on an instrument in the Shared FACS Facility obtained using NIH S10 Shared Instrument Grant S10RR025518-0. We thank Dr Young-June Kim for helpful comments and discussion on the manuscript.

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  1. Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    H-D Chae, B Mitton, N J Lacayo & K M Sakamoto

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  1. H-D Chae
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Correspondence to K M Sakamoto.

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Chae, HD., Mitton, B., Lacayo, N. et al. Replication factor C3 is a CREB target gene that regulates cell cycle progression through the modulation of chromatin loading of PCNA. Leukemia 29, 1379–1389 (2015). https://doi.org/10.1038/leu.2014.350

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