BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration.

BRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest.

Activation of β-Catenin Cooperates with Loss of Pten to Drive AR-Independent Castration-Resistant Prostate Cancer.

Inhibition of the androgen receptor (AR) is the main strategy to treat advanced prostate cancers. AR-independent treatment-resistant prostate cancer is a major unresolved clinical problem. Patients with prostate cancer with alterations in canonical WNT pathway genes, which lead to β-catenin activation, are refractory to AR-targeted therapies.

Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity which is linked to increased osteoclast activity.

Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate.

Increased T-cell Infiltration Elicited by Deletion in a -Deficient Mouse Model of Prostate Carcinogenesis.

Prostate cancer does not appear to respond to immune checkpoint therapies where T-cell infiltration may be a key limiting factor. Here, we report evidence that ablating the growth regulatory kinase can increase T-cell infiltration in an established -deficient mouse model of human prostate cancer. Mice that were doubly mutant in prostate tissue for and (prostate DKO) exhibited a markedly increased median survival with reduced tumor size and proliferation compared with control -mutant mice, the latter of which exhibited increased mRNA expression.

p300-mediated acetylation of COMMD1 regulates its stability, and the ubiquitylation and nucleolar translocation of the RelA NF-κB subunit.

Nucleolar sequestration of the RelA subunit of nuclear factor (NF)-κB is an important mechanism for regulating NF-κB transcriptional activity. Ubiquitylation, facilitated by COMMD1 (also known as MURR1), acts as a crucial nucleolar-targeting signal for RelA, but how this ubiquitylation is regulated, and how it differs from cytokine-mediated ubiquitylation, which causes proteasomal degradation of RelA, is poorly understood. Here, we report a new role for p300 (also known as EP300) in controlling stimulus-specific ubiquitylation of RelA, through modulation of COMMD1.

c-Src dependency of NSAID-induced effects on NF-κB-mediated apoptosis in colorectal cancer cells.

Long-term aspirin or related non-steroidal anti-inflammatory drugs (NSAIDs) ingestion can protect against colorectal cancer (CRC). NSAIDs have a pro-apoptotic activity and we have shown that stimulation of the nuclear factor-kappaB (NF-κB) pathway is a key component of this pro-apoptotic effect. However, the upstream pathways have yet to be fully elucidated.

Nucleolar targeting of RelA(p65) is regulated by COMMD1-dependent ubiquitination.

Stimulation of the NF-kappaB pathway can have proapoptotic or antiapoptotic consequences, and one mechanism that determines the outcome is the nuclear distribution of RelA. Certain stress stimuli induce nucleolar accumulation of RelA thereby mediating apoptosis, whereas others induce nucleoplasmic accumulation and inhibition of apoptosis. Here we investigated the mechanisms that regulate the nuclear distribution of RelA, specifically, the role of the ubiquitin/proteasome system.