Molecular cloning and functional characterization of the upstream promoter region of the human p73 gene.

The p73 gene encodes a protein that shares structural and functional homologies with the p53 tumor suppressor protein. To investigate the mechanism of transcriptional regulation of the p73 gene, we isolated a genomic DNA fragment spanning the 5' upstream region of the human p73 gene and characterized the promoter region. Unlike the p53 gene promoter, the human p73 gene promoter contained a putative TATA-box, and did not exhibit any extended homology to the p53 gene.

Molecular cloning and functional analysis of the murine bax gene promoter.

Bcl-2-associated X protein (Bax) is a proapoptotic protein and is suggested to have an important role in carcinogenesis. To investigate the mechanism of bax gene transcriptional regulation, we isolated and sequenced the genomic DNA fragment of the 5' flanking region of the murine bax gene, and subcloned its promoter region into a luciferase reporter construction. The murine bax promoter is TATA-less, and the sequence is only partially homologous to that of the human bax promoter.

Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter.

Smads are signal transducers for members of the transforming growth factor-beta (TGF-beta) superfamily. Upon ligand stimulation, receptor-regulated Smads (R-Smads) are phosphorylated by serine/threonine kinase receptors, form complexes with common-partner Smad, and translocate into the nucleus, where they regulate the transcription of target genes together with other transcription factors. Polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF) is a transcription factor complex composed of alpha and beta subunits.

The ubiquitous transcription factor NF-Y positively regulates the transcription of human p27Kip1 through a CCAAT box located in the 5-upstream region of the p27Kip1 gene.

Abnormally low levels of the cyclin-dependent kinase inhibitor p27Kip1 are found frequently in human carcinomas, and these levels correlate directly with both histological aggressiveness and patient mortality. p27Kip1 is haplo-insufficient for tumor suppression. Thus, p27Kip1 may be a useful molecule for the development of cancer therapies.