p53 suppresses cytokine induced, Stat5 mediated activation of transcription

Fritsche, Michael; Mundt, Maren; Merkle, Christian; Jähne, Ruth; Groner, Bernd

doi:10.1016/s0303-7207(98)00140-3

Cited by 25 publications

(20 citation statements)

References 55 publications

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“…It remains unknown whether ets-1 directly binds to the C-terminus of p53 or whether this interaction may be mediated by other proteins bridging the interaction between p53 and ets-1. However, our findings generally support the idea that the p53 C-terminus is crucial for the transcriptional repression mediated by wild-type p53 (Fritsche et al, 1998;Murphy et al, 1999;Hong et al, 2001). …”

Section: Discussionsupporting

confidence: 90%

Tumor suppressor p53 inhibits transcriptional activation of invasion gene thromboxane synthase mediated by the proto-oncogenic factor ets-1

et al. 2003

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Cancer formation and progression is a complex process determined by several mechanisms that promote cell growth, invasiveness, neo-angiogenesis, and render neoplastic cells resistant to apoptosis. The tumor suppressor p53 and the proto-oncogenic factor ets-1 are important regulators of such mechanisms. While it is well established that p53 and ets-1 influence various aspects of cell behavior by regulating the transcription of specific genes, little is known about the functional relationship between these transcription factors. We found that the gene encoding thromboxane synthase (TXSA), which we recently identified as a factor promoting invasion and resistance to apoptosis in gliomas, is a novel target gene for both p53 and ets-1. We demonstrate that p53 and ets-1 coregulate TXSA in an antagonistic and interrelated manner, with ets-1 being a potent transcriptional activator and p53 inhibiting ets-1-dependent transcription. Negative interference with ets-1 transcription requires functional p53 and is lost in mutant p53 proteins. We show that ets-1 and p53 associate physically in vitro and in vivo and that their interaction, rather than a direct binding of p53 to the TXSA promoter, is required for transcriptional repression of TXSA by wild-type p53. An important implication of our findings is that the loss of p53-mediated negative control over ets-1-dependent transcription may lead to the acquisition of an invasive phenotype in tumor cells.

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Section: Discussionsupporting

confidence: 90%

Tumor suppressor p53 inhibits transcriptional activation of invasion gene thromboxane synthase mediated by the proto-oncogenic factor ets-1

et al. 2003

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“…Alternatively, loss of p53 could increase the developmental window in the B-cell lineage in which activated STAT5 can manifest its pro-survival and proliferative capacities. Previous experiments have reported that wt p53 can counteract the transcriptional activation properties of STAT5 in transient reporter assays (Fritsche et al, 1998). It is therefore possible that the loss of p53 function contributes to STAT5A*-induced leukemogenesis by releasing STAT5A* transcriptional activity from a direct negative regulatory input by wt p53.…”

Section: Discussionmentioning

confidence: 97%

Constitutive STAT5 activation specifically cooperates with the loss of p53 function in B-cell lymphomagenesis

et al. 2006

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“…On the one hand, suppression of p53-mediated cell death by cytokines has been correlated with JAK-STAT activation (Quelle et al, 1998). On the other hand, p53 itself appears to be capable of negatively regulating certain STAT proteins (Fritsche et al, 1998). The observed binding of p53 to two members of a family of proteins which speci®cally inhibit STAT activity, GBP/PIAS1 and PIASy (Nelson and Maxwell, 1999), might shed some light on the above processes.…”

Section: Discussionmentioning

confidence: 99%