No abstract

No abstract

Cyclin B is a central regulator of transition from the G 2 phase of the cell cycle to mitosis. In mammalian cells two B-type cyclins have been characterised, cyclin B1 and B2. Both are expressed with a maximum in G 2 and their synthesis is mainly regulated on the transcriptional level. We show that a single cell cycle genes homology region, lacking a functional cell cycle-dependent element in tandem with it, contributes most of the cell cycle-dependent transcription from the cyclin B1 promoter. The coactivator p300 binds to the cyclin B1 promoter and synergises with the transcription factor NF-Y in activating transcription of cyclin B1. ß

The cdc25C phosphatase participates in regulating transition from the G2 phase of the cell cycle to mitosis by dephosphorylating cyclin-dependent kinase 1. The tumor suppressor p53 down-regulates expression of cdc25C as part of G2/M checkpoint control. Transcription of cdc25C oscillates during the cell cycle with no expression in resting cells and maximum transcription in G2. We had identified earlier a new mechanism of cell cycle-dependent transcription that is regulated by a cell cycle-dependent element (CDE) in conjunction with a cell cycle genes homology region (CHR). The human cdc25C gene was the first example. CDE/CHR tandem elements have since been found in promoters of many cell cycle genes. Here we show that the mouse cdc25C gene is regulated by a CHR but does not hold a CDE. Therefore, it is the first identified gene with CHR-dependent transcriptional regulation during the cell cycle not relying on a CDE located upstream of it. The CHR leads to repression of cdc25C transcription early in the cell cycle and directs a release of this repression in G2. Furthermore, we find that this CHR can cooperate in cell cycle-dependent transcription with elements placed directly upstream of it binding E2F, Sp1 or Sp3 transcription factors.

Maspin is a Class II tumor suppressor protein and plays a role in tumor growth by inhibiting cellular invasion and motility. It is a member of the serpin family of protease inhibitors and has been shown to reduce angiogenesis. Maspin gene expression can be upregulated by the tumor suppressor p53. We tested 7 p53-related proteins of the p63 and p73 families for their ability to induce maspin expression. The p63 splice form TAp63␥ can substitute for p53 in activating the maspin promoter. TAp63␥ activates the promoter through the same consensus site as p53. In the DLD-1 colorectal adenocarcinoma cell line, harboring a tet-off regulated transgene, induction of TAp63␥ leads to an upregulation of maspin mRNA from the chromosomal gene. With a short lag phase also maspin protein levels are elevated after induced TAp63␥ expression. To assess a potential function of p63-dependent maspin upregulation in tumors we followed expression of p53, p63 and maspin by immunohistochemistry in hepatocellular carcinomas. Two types of tumors with wild-type or mutant p53 were assayed. Interestingly, the majority of tumors expressing only a mutated and inactive p53 protein nonetheless stain positive for maspin, whereas these tumors were positive for p63 protein expression. In summary, we show that TAp63␥ can substitute for p53 in transcriptional activation of the maspin tumor suppressor gene. TAp63␥ employs the same DNA recognition site for this activation as p53. We observe expression patterns of p53, p63 and maspin proteins in tumor tissue that may indicate also a function of maspin induction by p63 in tumors.

No abstract

No abstract

No abstract