The c-myb protooncogene is preferentially expressed in hematopoietic cells and is required for cell cycle progression at the G1/S boundary. Because c-myb encodes a transcriptional activator that functions via DNA binding, it is likely that c-myb exerts its biological activity by regulating the transcription of genes required for DNA synthesis and cell cycle progression. One such gene, cdc2, encodes a 34-kDa serine-threonine kinase that appears to be required for G1/S transition in normal human T-lymphocytes. To determine whether c-myb is a transcriptional regulator of cdc2 expression, we subcloned a segment of a cdc2 human genomic clone containing extensive 5'-flanking sequences and part of the first exon. Sequence analysis revealed the presence of two closely spaced Myb binding sites that interact with bacterially synthesized Myb protein within a region extending from nucleotides -410 to -392 upstream of the transcription initiation site. A 465-base pair segment of 5'-flanking sequence containing these sites was linked to the CAT gene and had promoter activity in rodent fibroblasts. Cotransfection of this construct with a full-length human c-myb cDNA driven by the early simian virus 40 promoter resulted in a 6-8-fold enhancement of CAT activity that was abrogated by mutations in the Myb binding sites. These data suggest that c-myb participates in the regulation of cell cycle progression by activating the expression of the cdc2 gene.

c-myb transactivates cdc2 expression via Myb binding sites in the 5'-flanking region of the human cdc2 gene / Ku, Dh; Wen, Sc; Engelhard, A; Nicolaides, Nc; Lipson, Ke; Marino, Ta; Calabretta, Bruno. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 268:(1993), pp. 2255-2259. [10.1016/S0021-9258(18)53990-9]

c-myb transactivates cdc2 expression via Myb binding sites in the 5'-flanking region of the human cdc2 gene.

CALABRETTA, Bruno
1993-01-01

Abstract

The c-myb protooncogene is preferentially expressed in hematopoietic cells and is required for cell cycle progression at the G1/S boundary. Because c-myb encodes a transcriptional activator that functions via DNA binding, it is likely that c-myb exerts its biological activity by regulating the transcription of genes required for DNA synthesis and cell cycle progression. One such gene, cdc2, encodes a 34-kDa serine-threonine kinase that appears to be required for G1/S transition in normal human T-lymphocytes. To determine whether c-myb is a transcriptional regulator of cdc2 expression, we subcloned a segment of a cdc2 human genomic clone containing extensive 5'-flanking sequences and part of the first exon. Sequence analysis revealed the presence of two closely spaced Myb binding sites that interact with bacterially synthesized Myb protein within a region extending from nucleotides -410 to -392 upstream of the transcription initiation site. A 465-base pair segment of 5'-flanking sequence containing these sites was linked to the CAT gene and had promoter activity in rodent fibroblasts. Cotransfection of this construct with a full-length human c-myb cDNA driven by the early simian virus 40 promoter resulted in a 6-8-fold enhancement of CAT activity that was abrogated by mutations in the Myb binding sites. These data suggest that c-myb participates in the regulation of cell cycle progression by activating the expression of the cdc2 gene.
1993
268
2255
2259
c-myb transactivates cdc2 expression via Myb binding sites in the 5'-flanking region of the human cdc2 gene / Ku, Dh; Wen, Sc; Engelhard, A; Nicolaides, Nc; Lipson, Ke; Marino, Ta; Calabretta, Bruno. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 268:(1993), pp. 2255-2259. [10.1016/S0021-9258(18)53990-9]
Ku, Dh; Wen, Sc; Engelhard, A; Nicolaides, Nc; Lipson, Ke; Marino, Ta; Calabretta, Bruno
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/811742
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