Disease relevance of grim

• Amsacta moorei Entomopoxvirus inhibitor of apoptosis suppresses cell death by binding Grim and Hid [1].

High impact information on grim

• grim, a novel cell death gene in Drosophila [2].
• Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms [3].
• Drosophila p53: meeting the Grim Reaper [4].
• We found that mutations in peanut, which encodes a Drosophila homologue of ARTS, can dominantly suppress cell killing by Reaper, Hid and Grim, indicating that peanut acts downstream or in parallel to these [5].
• During apoptosis induction, Grim colocalizes with mitochondria and cytochrome c in a GH3-dependent but N-terminal- and caspase activity-independent manner [6].

Biological context of grim

• Mutations in the N-terminal region of Reaper, which displays sequence similarity to Hid and Grim, other Drosophila gene products correlated with the initiation of apoptosis, suggested that these residues might be functionally important [7].
• Unlike transiently transfected cells, inducible mammalian cell lines can sustain continuous expression of Grim and selective degradation of XIAP without undergoing apoptosis, demonstrating that down-regulation and antagonism of IAPs is not sufficient to cause apoptosis of mammalian cells [8].

Associations of grim with chemical compounds

• Conversely, targeted expression of GlcT-1 partially rescued cell death caused by the proapoptotic factors Reaper and Grim, suggesting that ceramide generation might be one signal pathway that executes the cell death program [9].

Regulatory relationships of grim

• Drosophila Bruce can potently suppress Rpr- and Grim-dependent but not Hid-dependent cell death [10].
• Synthetic Reaper and Grim N terminus peptides induced fast inactivation of Shaker-type K+ channels when applied to the cytoplasmic side of the channel that was qualitatively similar to the inactivation produced by other K+ channel inactivation particles [11].

Other interactions of grim

• Observations with Grim suggest that one mechanism by which these proteins produce a relative decrease in DIAP1 levels is to promote a general suppression of protein translation [3].
• These results indicate that Reaper and Grim, but not HID, can activate DCP-1 in vivo [12].
• Skl can also synergize with Grim to induce cell death in the Drosophila eye imaginal disc [13].
• Inhibition of the Drosophila CED-4/Apaf-1-related killer (ARK) homologue resulted in pronounced inhibition of stress-induced apoptosis, whereas loss of ARK did not protect the cells from Reaper- or Grim-induced cell death [14].
• Taken together, these results suggest that Grim stimulates the poly-ubiquitination and presumably degradation of Diap1 in a novel way by binding to UbcD1 but not to the UBC domain of dBruce as an E2 [15].

References