NDLI: Interaction of MCM7 and RACK1 for activation of MCM7 and cell growth.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhang, Xi-Yue Tang, Lang-Zhu Ren, Bao-Guo Yu, Yan P. Nelson, Joel Michalopoulos, George Luo, Jian-Hua
Description	Country affiliation: United States Author Affiliation: Zhang XY ( Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.)
Abstract	MCM7 is one of the pivotal DNA replication licensing factors in controlling DNA synthesis and cell entry into S phase. Its expression and DNA copy number are some of the most predictive factors for the growth and behavior of human malignancies. In this study, we identified that MCM7 interacts with the receptor for activated protein kinase C 1 (RACK1), a protein kinase C (PKC) adaptor, in vivo and in vitro. The RACK1 binding motif in MCM7 is located at the amino acid 221-248. Knocking down RACK1 significantly reduced MCM7 chromatin association, DNA synthesis, and cell cycle entry into S phase. Activation of PKC by 12-O-tetradecanoylphorbol-13-acetate dramatically decreased MCM7 DNA replication licensing and induced cell growth arrest. Activation of PKC induced redistribution of RACK1 from nucleus to cytoplasm and decreased RACK1-chromatin association. The MCM7 mutant that does not bind RACK1 has no DNA replication licensing or oncogenic transformation activity. As a result, this study demonstrates a novel signaling mechanism that critically controls DNA synthesis and cell cycle progression.
File Format	HTM / HTML
ISSN	00029440
e-ISSN	15252191
DOI	10.1016/j.ajpath.2012.11.020
Journal	The American Journal of Pathology
Issue Number	3
Volume Number	182
Language	English
Publisher	Elsevier (on behalf of the American Society for Investigative Pathology)
Publisher Date	2013-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Chromatin Dna-binding Proteins Cell Proliferation Gtp-binding Proteins Receptors, Cell Surface Discipline Pathology Biosynthesis Minichromosome Maintenance Complex Component 7 Metabolism Nuclear Proteins Cell Transformation, Neoplastic Models, Biological Neoplasm Proteins S Phase Cell Line, Tumor Protein Binding Enzyme Activation Cell Cycle Proteins Protein Kinase C
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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Interaction of MCM7 and RACK1 for activation of MCM7 and cell growth.

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