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In mammalian cells, the MYC oncoprotein binds to thousands of promoters. During mitogenic stimulation of primary lymphocytes, MYC promotes an increase in the expression of virtually all genes. In contrast, MYC-driven tumour cells differ from normal cells in the expression of specific sets of up- and downregulated genes that have considerable prognostic(More)
The Myc oncoprotein represses initiator-dependent transcription through the POZ domain transcription factor Miz-1. We now show that transactivation by Miz-1 is negatively regulated by association with topoisomerase II binding protein (TopBP1); UV irradiation downregulates expression of TopBP1 and releases Miz-1. Miz-1 binds to the p21Cip1 core promoter in(More)
The Myc oncoprotein is a transcription factor that can both activate and repress genes. Transcriptional activation by Myc is well understood, but, by contrast, the mechanisms through which Myc represses transcription have remained elusive. Recent evidence suggests that complex formation by Myc with a zinc-finger transcription factor, Miz-1, plays an(More)
Myc plays a key role in homeostasis of the skin. We show that Miz1, which mediates Myc repression of gene expression, is expressed in the epidermal basal layer. A large percentage of genes regulated by the Myc-Miz1 complex in keratinocytes encode proteins involved in cell adhesion, and some, including the alpha6 and beta1 integrins, are directly bound by(More)
Neuroblastoma is the most common extracranial solid tumor of childhood. One important factor that predicts a favorable prognosis is the robust expression of the TRKA and p75NTR neurotrophin receptor genes. Interestingly, TRKA and p75NTR expression is often attenuated in aggressive MYCN-amplified tumors, suggesting a causal link between elevated MYCN(More)
The Myc-associated zinc-finger protein, Miz1, activates transcription of the p21cip1 gene in response to UV irradiation. Miz1 associates with topoisomerase II binding protein1 (TopBP1), an essential activator of the Atr kinase. We show here that Miz1 is required for the recruitment of a fraction of TopBP1 to chromatin, for the protection of TopBP1 from(More)
The cellular levels of the Myc oncoprotein are critical determinants of cell proliferation, cell growth and apoptosis and are tightly regulated by external growth factors. Levels of Myc oncoprotein also decline in response to intracellular stress signals such as DNA damage. We show here that this decline is in part due to proteasomal degradation and that it(More)
Deregulated expression of MYC contributes to the genesis of multiple human tumours. The encoded protein, MYC, functions through the transcriptional regulation of large numbers of target genes. Recent publications show that MYC is closely involved in DNA replication and the checkpoint processes that monitor progress through the S phase, and suggest that(More)
The transcription factor Miz1 is required for DNA-damage-induced cell-cycle arrest. We have now identified 14-3-3eta as a gene that inhibits Miz1 function through interaction with its DNA binding domain. Binding of 14-3-3eta to Miz1 depends on phosphorylation by Akt and regulates the recovery of cells from arrest after DNA damage. Miz1 has two functions in(More)
We used the Sleeping Beauty (SB) transposable element as a tool to probe transposon-host cell interactions in vertebrates. The Miz-1 transcription factor was identified as an interactor of the SB transposase in a yeast two-hybrid screen. Through its association with Miz-1, the SB transposase down-regulates cyclin D1 expression in human cells, as evidenced(More)