Document Detail

CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle.
MedLine Citation:
PMID:  12716909     Owner:  NLM     Status:  MEDLINE    
The Gadd45 family of proteins includes Gadd45alpha, MyD118/Gadd45beta, and CR6/OIG37/Gadd45gamma. These proteins play important roles in maintaining genomic stability and in regulating the cell cycle. This study reports the cloning of a novel protein called CR6-interacting factor 1 (CRIF1) which interacts with Gadd45alpha, MyD118/Gadd45beta, and CR6/OIG37/Gadd45gamma. CRIF1 binds specifically to the Gadd45 family proteins, as determined by an in vitro glutathione S-transferase pull-down assay and an in vivo mammalian cell two-hybrid assay along with coimmunoprecipitation assays. CRIF1 mRNA is highly expressed in the thyroid gland, heart, lymph nodes, trachea, and adrenal tissues. CRIF1 localizes exclusively to the nucleus and colocalizes with Gadd45gamma. Recombinant CRIF1 inhibits the histone H1 kinase activity of immunoprecipitated Cdc2-cyclin B1 and Cdk2-cyclin E, and the inhibitory effects were additive with Gadd45 proteins. Overexpression of CRIF1 increases the percentage of cells in G1, decreases the percentage of cells in S phase, and suppresses growth in NIH3T3 cells. The down-regulation of endogenous CRIF1 by the transfection of the small interfering RNA duplexes resulted in the inactivation of Rb by phosphorylation and decreased the G1 phase cell populations. Expression of CRIF1 is barely detectable in adrenal adenoma and papillary thyroid cancer and much lower than in adjacent normal tissue. The results presented here suggest that CRIF1 is a novel nuclear protein that interacts with Gadd45 and may play a role in negative regulation of cell cycle progression and cell growth.
Hyo Kyun Chung; Yong-Weon Yi; Neon-Cheol Jung; Daegun Kim; Jae Mi Suh; Ho Kim; Ki Cheol Park; Jung Hun Song; Dong Wook Kim; Eun Suk Hwang; Soo-Hyun Yoon; Young-Seuk Bae; Jin Man Kim; Insoo Bae; Minho Shong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2003-04-25
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-07-21     Completed Date:  2003-08-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  28079-88     Citation Subset:  IM    
Laboratory of Endocrine Cell Biology, National Research Laboratory Program, Chungnam National University School of Medicine, Daejeon 301-721 Korea.
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MeSH Terms
3T3 Cells
Amino Acid Sequence
Base Sequence
COS Cells
Carrier Proteins / metabolism*
Cell Cycle
Cell Cycle Proteins / biosynthesis*,  chemistry
Cell Division
DNA, Complementary / metabolism
G1 Phase
Glutathione Transferase / metabolism
Intracellular Signaling Peptides and Proteins*
Microscopy, Fluorescence
Molecular Sequence Data
Nuclear Proteins
Precipitin Tests
Protein Binding
Proteins / metabolism*
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Recombinant Proteins / metabolism
Retinoblastoma Protein / metabolism
S Phase
Sequence Homology, Amino Acid
Time Factors
Tissue Distribution
Tumor Cells, Cultured
Two-Hybrid System Techniques
Reg. No./Substance:
0/Carrier Proteins; 0/Cell Cycle Proteins; 0/DNA, Complementary; 0/GADD45 protein; 0/GADD45G protein, human; 0/GADD45GIP1 protein, human; 0/Intracellular Signaling Peptides and Proteins; 0/Nuclear Proteins; 0/Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Recombinant Proteins; 0/Retinoblastoma Protein; EC Transferase

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