ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97.

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology.

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97.

The t(X,17) chromosomal translocation, generating the ASPSCR1-TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCC), frustrating efforts to identify therapeutic targets for these rare cancers. Proteomic analysis showed that VCP/p97, an AAA+ ATPase with known segregase function, was strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1-TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1-TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology.

A Role for SMARCB1 in Synovial Sarcomagenesis Reveals That SS18-SSX Induces Canonical BAF Destruction.

Reduced protein levels of SMARCB1 (also known as BAF47, INI1, SNF5) have long been observed in synovial sarcoma. Here, we show that combined genetic loss with expression in mice synergized to produce aggressive tumors with histomorphology, transcriptomes, and genome-wide BAF-family complex distributions distinct from alone, indicating a defining role for SMARCB1 in synovial sarcoma. silencing alone in mesenchyme modeled epithelioid sarcomagenesis.

SKP2 My Lou, My Darling.

Myxofibrosarcoma and undifferentiated pleomorphic sarcoma (UPS) lack specific molecular underpinnings, show high rates of metastasis, and display limited responsiveness to current therapies, making them challenging cancers both to treat and to study. It has been noted that MFS and UPS frequently lose function of the tumor suppressor genes and In this issue of , Li and colleagues demonstrate that proliferation in RB1- and TP53-deficient MFS and UPS depends on SKP2; inhibiting SKP2 with the neddylation inhibitor, pevonedistat, halts tumor growth in a panel of patient-derived xenografts. This renders the oncogenic protein SKP2 a promising therapeutic target.

Erythromycin treatment hinders the induction of oral tolerance to fed ovalbumin.

The mucosal immune system is constantly exposed to antigen, whether it be food antigen, commensal bacteria, or harmful antigen. It is essential that the mucosal immune system can distinguish between harmful and non-harmful antigens, and initiate an active immune response to clear the harmful antigens, while initiating a suppressive immune response (tolerance) to non-harmful antigens. Oral tolerance is an immunologic hyporesponsiveness to an orally administered antigen and is important in preventing unnecessary gastrointestinal tract inflammation, which can result in a number of autoimmune and hypersensitivity diseases.

EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling.

Epidermal growth factor (EGF) family peptides are ligands for the EGF receptor (EGFR). Here, we elucidate functional differences among EGFR ligands and mechanisms underlying these distinctions. In 32D/EGFR myeloid and MCF10A breast cells, soluble amphiregulin (AR), transforming growth factor alpha (TGFα), neuregulin 2 beta, and epigen stimulate greater EGFR coupling to cell proliferation and DNA synthesis than do EGF, betacellulin, heparin-binding EGF-like growth factor, and epiregulin.