Organization of the Chick CDC37 Gene*

CDC37 and the chaperone protein, Hsp90, form a complex that binds to several kinases, resulting in stabilization and promotion of their activity. CDC37 also binds DNA and glycosaminoglycans in a sequence-specific manner. In this study, we further characterize chick CDC37 and examine the organization of the CDC37 gene. Chick CDC37 is a ∼50-kDa protein encoded by an mRNA of ∼1.7 kilobases. The CDC37 gene is ∼8.5 kilobases and contains 8 exons and 7 introns of various sizes. The presumptive promoter and 5′-flanking regions contain an E2 box and consensus binding sites for SP1, for the S8 homeodomain protein, and for two zinc finger clusters within the myeloid progenitor transcription factor, MZF1. Particularly striking is a ∼470-base pair region composed of a highly repetitive 10–11-base pair sequence, (T/C)gCTAT(A/G)GGG(A/T) (where g represents the additional G present in the 11-base pair sequence). This region includes 15 copies of the sequence, TATGGGGA, which conforms to the DNA consensus sequence recognized by one of the zinc finger clusters in MZF1. These findings emphasize the potential importance of CDC37 in regulation of cellular behavior during tissue development and reorganization.

[1]  S. Lindquist,et al.  Cdc 37 is a molecular chaperone with specific functions in signal transductlon , 2007 .

[2]  J. V. Vanden Heuvel,et al.  A 50 kilodalton protein associated with raf and pp60(v-src) protein kinases is a mammalian homolog of the cell cycle control protein cdc37. , 1997, Biochemistry.

[3]  T. Giddings,et al.  The Yeast CDC37 Gene Interacts with MPS1 and Is Required for Proper Execution of Spindle Pole Body Duplication , 1997, The Journal of cell biology.

[4]  T. Ozaki,et al.  Interaction of rat Cdc37-related protein with retinoblastoma gene product. , 1996, DNA and cell biology.

[5]  R. Kobayashi,et al.  Physical Interaction of Mammalian CDC37 with CDK4* , 1996, The Journal of Biological Chemistry.

[6]  T. Ozaki,et al.  Specific interaction of pRB with a rat genomic DNA fragment, REC11. , 1996, Biochemical and biophysical research communications.

[7]  F. Boschelli,et al.  CDC37 is required for p60v-src activity in yeast. , 1996, Molecular biology of the cell.

[8]  J. Harper,et al.  Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. , 1996, Genes & development.

[9]  T. Ozaki,et al.  Molecular cloning and cell cycle-dependent expression of a novel gene that is homologous to cdc37. , 1995, DNA and cell biology.

[10]  B. Toole,et al.  A Novel Glycosaminoglycan-binding Protein Is the Vertebrate Homologue of the Cell Cycle Control Protein, Cdc37 (*) , 1995, The Journal of Biological Chemistry.

[11]  I. Herskowitz,et al.  Cdc37 is required for association of the protein kinase Cdc28 with G1 and mitotic cyclins. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Y. Nabeshima,et al.  The delta-crystallin enhancer-binding protein delta EF1 is a repressor of E2-box-mediated gene activation , 1994, Molecular and cellular biology.

[13]  G. Rubin,et al.  Mutations in Hsp83 and cdc37 impair signaling by the sevenless receptor tyrosine kinase in Drosophila , 1994, Cell.

[14]  R. Hromas,et al.  Characterization of the DNA-binding properties of the myeloid zinc finger protein MZF1: two independent DNA-binding domains recognize two DNA consensus sequences with a common G-rich core , 1994, Molecular and cellular biology.

[15]  V. Hascall,et al.  Nuclear localization of glycosaminoglycans in rat ovarian granulosa cells. , 1994, The Journal of biological chemistry.

[16]  R. Savani,et al.  Identification of a common hyaluronan binding motif in the hyaluronan binding proteins RHAMM, CD44 and link protein. , 1994, The EMBO journal.

[17]  R. Jove,et al.  Raf exists in a native heterocomplex with hsp90 and p50 that can be reconstituted in a cell-free system. , 1993, The Journal of biological chemistry.

[18]  W. Pratt.  The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. , 1993, The Journal of biological chemistry.

[19]  R. D. Jong,et al.  DNA-binding specificity of the S8 homeodomain , 1993 .

[20]  R. Jackson,et al.  Trans-repressor activity of nuclear glycosaminoglycans on Fos and Jun/AP-1 oncoprotein-mediated transcription , 1992, The Journal of cell biology.

[21]  G. Perdew,et al.  Evidence that the 90-kDa heat shock protein (HSP90) exists in cytosol in heteromeric complexes containing HSP70 and three other proteins with Mr of 63,000, 56,000, and 50,000. , 1991, The Journal of biological chemistry.

[22]  D. Baltimore,et al.  B-cell- and myocyte-specific E2-box-binding factors contain E12/E47-like subunits , 1991, Molecular and cellular biology.

[23]  B. Toole.  Proteoglycans and Hyaluronan in Morphogenesis and Differentiation , 1991 .

[24]  Carl O. Pabo,et al.  Crystal structure of an engrailed homeodomain-DNA complex at 2.8 Å resolution: A framework for understanding homeodomain-DNA interactions , 1990, Cell.

[25]  R. U. Margolis,et al.  Immunoelectron microscopic localization of hyaluronic acid-binding region and link protein epitopes in brain , 1989, The Journal of cell biology.

[26]  H. Conrad,et al.  Correlations between heparan sulfate metabolism and hepatoma growth , 1989, Journal of cellular physiology.

[27]  M. Frohman,et al.  Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[28]  P. Prehm,et al.  Increased hyaluronate synthesis is required for fibroblast detachment and mitosis. , 1986, The Biochemical journal.

[29]  S. Reed,et al.  Nucleotide sequence of the yeast cell division cycle start genes CDC28, CDC36, CDC37, and CDC39, and a structural analysis of the predicted products. , 1986, Nucleic acids research.

[30]  N. Fedarko,et al.  Transport of heparan sulfate into the nuclei of hepatocytes. , 1986, The Journal of biological chemistry.

[31]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[32]  J. Brugge,et al.  Interaction between the Rous sarcoma virus transforming protein and two cellular phosphoproteins: analysis of the turnover and distribution of this complex , 1983, Molecular and cellular biology.

[33]  J. Bishop,et al.  Transit of pp60v-src to the plasma membrane. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[34]  J. Brugge,et al.  Rous sarcoma virus-induced phosphorylation of a 50,000-molecular weight cellular protein , 1982, Nature.

[35]  J. Brugge,et al.  The specific interaction of the Rous sarcoma virus transforming protein, pp60src, with two cellular proteins , 1981, Cell.

[36]  S. Reed.  The selection of S. cerevisiae mutants defective in the start event of cell division. , 1980, Genetics.

[37]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.