In Science this week, researchers at Harvard Medical School and elsewhere report their use of "large-scale quantitative phosphoproteomics experiments to define the signaling networks downstream of mTORC1 and mTORC2. The team characterized one mTORC1 substrate, the growth factor receptor-bound protein 10, or Grb10, and found that its expression was "frequently down-regulated in various cancers." Further, the team says that Grb10 loss seems to be mutually exclusive with loss of the tumor suppressor PTEN, "suggesting that Grb10 might be a tumor suppressor regulated by mTORC1."
A team led by investigators at the Whitehead Institute reports in this week's Science how its interrogation of the mammalian target of rapamycin-regulated phosphoproteome revealed "a mechanism of mTORC1-mediated inhibition of growth factor signaling. Using quantitative mass spectrometry the team "defined the mTOR-regulated phosphoproteome … and characterized the primary sequence motif specificity of mTOR using positional scanning peptide libraries." Overall, the Whitehead-led team says its study "clarifies how mTORC1 inhibits growth factor signaling."
Another team from Harvard Medical School reports its identification of the previously uncharacterized protein RHINO and its involvement in ataxia telangiectasia and Rad3-related, or ATR, signaling. It was during a DNA damage response screen — in which it searched for "cells that lacked damage-induced cell cycle arrest" — that the team observed RHINO's recruitment by the Rad9-Rad1-Hus1 complex to promote Chk1 activation. "We suggest that RHINO functions together with the 9-1-1 [Rad9-Rad1-Hus1] complex and TopBP1 to fully activate ATR," the authors write.
Over in Science Translational Medicine, investigators at the Baylor College of Medicine and elsewhere this week report their development of a "protein interaction network that identified hundreds of new interactions among proteins encoded by ASD [autism spectrum disorder]-associated genes." The team says it was surprised to find "high connectivity between SHANK and TSC1, previously implicated in syndromic autism, suggesting that common molecular pathways underlie autistic phenotypes in distinct syndromes." Further, the team also identified "three de novo lesions ... that involve three network genes (NECAB2, PKM2, and FLNA)" in individuals with idiopathic ASD, it reports.