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Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and(More)
Fbw7 is a ubiquitin-ligase that targets several oncoproteins for proteolysis, but the full range of Fbw7 substrates is not known. Here we show that by performing quantitative proteomics combined with degron motif searches, we effectively screened for a more complete set of Fbw7 targets. We identify 89 putative Fbw7 substrates, including several(More)
Both the canonical and noncanonical nuclear factor κB (NF-κB) pathways have been linked to tumorigenesis. However, it remains unknown whether and how the 2 signaling pathways cooperate during tumorigenesis. We report that inhibition of the noncanonical NF-κB pathway significantly delays tumorigenesis mediated by the viral oncoprotein Tax. One function of(More)
The canonical Wnt signaling pathway (or Wnt/β-catenin pathway) plays a pivotal role in embryonic development and adult homeostasis; deregulation of the Wnt pathway contributes to the initiation and progression of human diseases including cancer. Despite its importance in human biology and disease, how regulation of the Wnt/β-catenin pathway is achieved(More)
Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATL), whereas the highly related HTLV-2 is not associated with ATL or other cancers. In addition to ATL leukemogenesis, studies of the HTLV viruses also provide an exceptional model for understanding basic pathogenic mechanisms of virus-host(More)
Activation of the NF-κB transcription factors by the viral protein Tax plays a vital role in the pathogenesis of diseases associated with human T-cell lymphotropic virus type I (HTLV-I). The Tax oncoprotein undergoes constitutive K63-linked ubiquitination and sumoylation; however, the roles and molecular mechanisms of these post-translational modifications(More)
Recent studies suggest that high expression of the proinflammatory cytokine IL6 is associated with poor survival of lung cancer patients. Accordingly, IL6 has been a target of great interest for lung cancer therapy. However, the role of IL6 in lung cancer has not been determined yet. Here, we demonstrate that IL6 plays opposite roles in the initiation and(More)
Signal transducer and activator of transcription 3 (STAT3) is linked to multiple cancers, including pulmonary adenocarcinoma. However, the role of STAT3 in lung cancer pathogenesis has not been determined. Using lung epithelial-specific inducible knockout strategies, we demonstrate that STAT3 has contrasting roles in the initiation and growth of both(More)
Nuclear factor-κB (NF-κB) is generally believed to be pro-tumorigenic. Here we report a tumor-suppressive function for NF-κB1, the prototypical member of NF-κB. While NF-κB1 downregulation is associated with high lung cancer risk in humans and poor patient survival, NF-κB1-deficient mice are more vulnerable to lung tumorigenesis induced by the smoke(More)
Although the mechanisms by which the HTLV-I Tax oncoprotein activates the two NF-B signaling pathways have been well studied, there is still no convincing evidence demonstrating a functional role for NF-B in the Tax-mediated tumorigenesis or HTLV-I-mediated adult T-cell leukemia/lymphoma (ATL). Moreover, how Tax is negatively regulated by cellular factors(More)