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The cyclin-dependent kinase inhibitor p21WAF1/CIP1 is a key regulator of cell-cycle progression and its expression is tightly regulated at the level of transcription and by proteasome-dependent proteolysis. The turnover of p21WAF1/CIP1 by proteasomes does not always require the ubiquitylation of p21WAF1/CIP1 suggesting that there could be an alternative(More)
CtBP has been shown to be a highly conserved corepressor of transcription. E1A and all the various transcription factors to which CtBP binds contain a conserved PLDLS CtBP-interacting domain, and EBNA3C includes a PLDLS motif (amino acids [aa] 728 to 732). Here we show that EBNA3C binds to CtBP both in vitro and in vivo and that the interaction requires an(More)
The Epstein-Barr virus (EBV) is associated with the development of different malignancies. In the last few years, EBV has been detected in a subset of breast tumors. The EBV genome was detected by PCR and Southern-blot analysis and identification of the infected cells was determined using different in situ methods. EBV has detected more frequently in(More)
Inactivation of retinoblastoma protein (Rb) plays a critical role in the development of human malignancies. It has been shown that Rb is degraded through a proteasome-dependent pathway, yet the mechanism is largely unclear. MDM2 is frequently found amplified and overexpressed in a variety of human tumors. In this study, we find that MDM2 promotes Rb(More)
Low density lipoprotein receptor-related protein 5 (LRP5) has been identified as a Wnt co-receptor involved in the activation of the beta-catenin signaling pathway. To improve our understanding of the molecular mechanisms by which LRP5 triggers the canonical Wnt signaling cascade, we have screened for potential partners of LRP5 using the yeast two-hybrid(More)
EBNA3C can specifically repress the expression of reporter plasmids containing EBV Cp latency-associated promoter elements. Cp is normally the main promoter for EBNA mRNA initiation, so it appears that EBNA3C contributes to a negative autoregulatory control loop. By mutational analysis it was previously established that this repression is consistent with(More)
Expression of EBNA3C is essential for the immortalization of B cells by EBV in vitro and, in co-operation with activated ras, EBNA3C has oncogenic activity in primary rodent fibroblasts. This suggested that this viral oncoprotein might disrupt the cyclin/CDK-pRb-E2F pathway, which regulates cell cycle progression at the restriction point (R-point) in G1 of(More)
A yeast two-hybrid screen using EBNA3C as bait revealed an interaction between this Epstein-Barr virus (EBV)-encoded nuclear protein and the C8 (alpha7) subunit of the human 20S proteasome. The interaction was confirmed by glutathione S-transferase (GST) pull-down experiments and these also revealed that the related proteins EBNA3A and EBNA3B can bind(More)
Activation of the Wnt signaling cascade plays a pivotal role during development and in various disease states. Wnt signals are transduced by seven-transmembrane Frizzled (Fz) proteins and the single-transmembrane LDL-receptor-related proteins 5 or 6 (LRP5/6). Genetic mutations resulting in a loss or gain of function of LRP5 in humans lead to osteopenia and(More)
Dickkopf-1 (Dkk1) protein is a secreted inhibitor of canonical Wnt signaling and modulates that pathway during embryonic development. It is also implicated in several diseases and hence Dkk1 is a potential target for therapeutic intervention. In the present study 6His-tagged Dkk1 expression and secretion was assessed in five mammalian cell types. Only(More)