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UCH-L1 bypasses mTOR to promote protein biosynthesis and is required for MYC-driven lymphomagenesis in mice

Thursday, December 13, 2018 -- The mechanistic target of rapamycin (mTOR) is a central regulator of cellular proliferation and metabolism. Depending on its binding partners, mTOR is at the core of 2 complexes that either promote protein biosynthesis (mTOR complex 1; mTORC1) or provide survival and proliferation signals (mTORC2). Protein biosynthesis downstream of mTORC1 plays an important role in MYC-driven oncogenesis with translation inhibitors garnering increasing therapeutic attention. The germinal center B-cell oncogene UCHL1 encodes a deubiquitinating enzyme that regulates the balance between mTOR complexes by disrupting mTORC1 and promoting mTORC2 assembly. While supporting mTORC2-dependent growth and survival signals may contribute to its role in cancer, the suppression of mTORC1 activity is enigmatic, as its phosphorylation of its substrate 4EBP1 promotes protein biosynthesis. To

Survivors of childhood Hodgkin lymphoma face ongoing risk for solid cancers

Monday, December 17, 2018 -- Adults who survived childhood Hodgkin lymphoma have a continued risk for subsequent malignant neoplasms, according to findings published in Cancer.Researchers observed particularly elevated risks by age 50 years for breast, lung, colorectal and thyroid cancers among high-risk subgroups.“These findings support the need for continued surveillance of patients with Hodgkin lymphoma, regardless of the era in which they were treated,” Smita Bhatia, MD, MPH, professor and vice chair of outcomes for pediatrics and director of the school of medicine institute for cancer outcomes at