https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20844 TP53INP1 was found to be one of the genes most significantly repressed by HDAC2 and N-Myc according to Affymetrix microarray gene expression datasets. HDAC2 and N-Myc reduced TP53INP1 gene expression by direct binding to the TP53INP1 gene promoter, leading to transcriptional repression of TP53INP1, p53 protein de-phosphorylation at serine 46, neuroblastoma cell proliferation and survival. Moreover, low levels of TP53INP1 expression in human neuroblastoma tissues correlated with high levels of N-Myc expression and poor patient outcome, and the BET bromodomain inhibitors JQ1 and I-BET151 reduced N-Myc expression and reactivated TP53INP1 expression in neuroblastoma cells. These findings identify TP53INP1 repression as an important co-factor for N-Myc oncogenesis, and provide further evidence for the potential application of BET bromodomain inhibitors in the therapy of N-Myc-induced neuroblastoma.]]> Wed 11 Apr 2018 13:01:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27776 Thu 28 Oct 2021 13:04:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36614 Thu 28 Oct 2021 12:37:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52222 Thu 05 Oct 2023 10:30:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1006 Sat 24 Mar 2018 08:29:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40592 Mon 08 Aug 2022 15:18:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38689 FAT1 gene was cloned over 20 years ago, but there has only been an incremental understanding of its functional role in cancer and developmental disorders. FAT1 is highly expressed in a large proportion of cases of T-cell acute lymphoblastic leukemia (T-ALL) and B-cell ALL compared to their normal counterparts suggesting an oncogenic function. Conversely, the FAT1 gene is also recurrently mutated in a small subset of TALL cases and also in chronic lymphocytic leukemia. Functionally, the FAT1 cadherin has been implicated in Wnt signaling, hippo signaling and more recently mitochondrial function which together suggests a role outside the classical cadherin function in regulating cell-cell adhesion. Here we show that T-ALL cell lines and clinical samples express a unique N-terminal truncated FAT1 mRNA transcript that generates a protein from a novel transcriptional start site within a retained intronic sequence. This novel transcript is regulated independently of full-length FAT1 and results in the expression of a truncated protein lacking almost the entire extracellular domain of FAT1. Significantly, this truncated protein is a novel biomarker for T-ALL and was found to cooperate with NOTCH in driving T-ALL in vivo, suggesting that in the context of T-ALL, this truncated protein may act as an oncogene.]]> Fri 12 Aug 2022 13:35:10 AEST ]]>