Deubiquitylatinase inhibitor b-AP15 induces c-Myc-Noxa-mediated apoptosis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in east Asia. However, the molecular mechanism underlying its progression remains unclear. The ubiquitin-proteasome system (UPS) is a central mechanism for protein degradation and turnover.

Targeting the overexpressed USP7 inhibits esophageal squamous cell carcinoma cell growth by inducing NOXA-mediated apoptosis.

Increasing evidence suggests that deubiquitinase USP7 participates in tumor progression by various mechanisms and serves as a potential therapeutic target. However, its expression and role in esophageal cancer remains elusive; the anti-cancer effect by targeting USP7 still needs to be investigated. Here, we reported that USP7 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent tissues, implying that USP7 was an attractive anticancer target of ESCC.

A potential regulatory role for mRNA secondary structures within the prothrombin 3'UTR.

The distal 3'UTR of prothrombin mRNA exhibits significant sequence heterogeneity reflecting an inexact 3'-cleavage/polyadenylation reaction. This same region encompasses a single-nucleotide polymorphism that enhances the normal post-transcriptional processing of nascent prothrombin transcripts. Both observations indicate the importance of 3'UTR structures to physiologically relevant properties of prothrombin mRNA.

Undetectable transcription of cap in a clinical AAV vector: implications for preformed capsid in immune responses.

In a gene therapy clinical trial for hemophilia B, adeno-associated virus 2 (AAV2) capsid-specific CD8(+) T cells were previously implicated in the elimination of vector-transduced hepatocytes, resulting in loss of human factor IX (hFIX) transgene expression. To test the hypothesis that expression of AAV2 cap DNA impurities in the AAV2-hFIX vector was the source of epitopes presented on transduced cells, transcription of cap was assessed by quantitative reverse transcription-PCR (Q-RT-PCR) following transduction of target cells with the vector used in the clinical trial. Transcriptional profiling was also performed for residual Amp(R), and adenovirus E2A and E4.

Transcriptional regulation of mouse MARCKS promoter in immortalized hippocampal cells.

Mouse MARCKS is a prominent myristoylated alanine-rich C kinase substrate implicated in brain development, calcium/calmodulin signaling, and membrane cytoskeletal restructuring, and is developmentally regulated in a cell- and tissue-specific fashion. In this study, transcriptional regulation of mouse MARCKS promoter in the neuronally derived immortalized hippocampal cells (HN33) was examined for a portion of 5'-flanking genomic sequence from -993 to +1 relative to the translation start site. Transfection experiments carried out in this neural cell line identified, for the first time, that the distal promoter segment from -993 to -713 plays a crucial role as an enhancer/activator element in the up-regulation of the basal transcription activity driven by MARCKS core promoter sequence.

Expression of the neurotrophin receptor TrkA down-regulates expression and function of angiogenic stimulators in SH-SY5Y neuroblastoma cells.

Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors. Mechanisms regulating the expression of angiogenic factors in tumor cells are largely unknown. High expression of the neurotrophin receptor TrkA in neuroblastomas (NBs) is associated with a favorable prognosis, whereas TrkB is mainly expressed on aggressive, MYCN-amplified NBs.