Inhibition of mTORC1 by Astrin and Stress Granules Prevents Apoptosis in Cancer Cells

Abstract

During the preparation of figures for the above article, we inadvertently rotated the astrin blot in Figure 3F by 180 , and we inserted incorrect images in Figures 3H and 4F. The correct and incorrect images were derived from experiments conducted in parallel and are quite similar in appearance. We mislabeled them when we retrieved them for figure preparation. In Figure 3H, we inserted an incorrect image for astrin. In Figure 4F, we inserted an incorrect image for raptor-astrin PLA under arsenite treatment in the right panel. Furthermore, we used DAPI for nuclear staining in PLA but instead indicated Hoechst in the figure legends. These errors do not affect the results or interpretation of any of these experiments. The corrected images have been inserted into the figures below, and the figures and figure legends of PLA panels have been corrected online. We regret these errors and apologize for the inconvenience that they may have caused.

Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress

“…However, others have reported that stress granules can form in the presence of H 2 O 2 in an eIF2␣-independent manner (44,92 Stress granule formation reduces the development of reactive oxygen species, thereby inhibiting apoptosis and favoring repair (93). The YB-1 protein has been proposed to play a key role in translation regulation by interacting with quadruplexes.…”

mRNP granules

“…Intriguing examples of the latter, unrelated to direct regulation of mRNPs, concerns localization of signaling factors in stress granules. Specifically, localization of factors such as RACK1, 85 TRAF2, 86 and TORC1 87,88 in stress granules affects signaling outcomes in response to cellular stress or extracellular signaling. However, since mRNPs form the primary component of these granules, most described or hypothesized roles have focused on possible effects on mRNA, examples of which are discussed below.…”

“…106 4E-BPs localize in P-bodies and stress granules, as does TORC1 itself (the main TOR kinase complex). 87,88 More specific regulation of mRNAs usually involves proteins that bind cis elements in particular mRNAs, which then directly, or via recruitment of additional factors, disrupt the formation of productive initiation complexes. A common mechanism is impaired assembly of the eIF4E-eIF4G capbinding complex, which facilitates recruitment of small ribosomal subunits to mRNAs.…”

“…Stress granules are also upregulated in some cancers, 133 and may facilitate cancer cell survival. 88,134 Impaired localization of neuronal transport granules and translational control of their mRNPs are some of the mechanisms proposed to explain conditions such as spinal muscular atrophy and Fragile X syndrome (for review, see ref. 135).…”

“…For example, disease alleles of TDP-43 impair transport along axons of particular neuronal transport granules. 149 Finally, aberrant sequestration of signaling factors in stress granules, which can alter growth and apoptotic decisions in several cases [85][86][87][88] could also be critical to disease progression. Determining the causes of cellular toxicity, and why cell types such as neurons appear especially susceptible to mutations that affect mRNP granules, are outstanding questions that now lie before the field.…”