In flies, hemocyte-specific expression of an activated form of RAS (Dmel\Ras85DV12) in combination with knockdown of either scrib or l(2)gl results in dramatic increases in hemocyte number (in the range of 100-fold). The animals typically die during the larval or pupal stage. Phenotypes reminiscent of cachexia are observed. Responses to infectious agents have been assessed.
The constitutively active Ras85D mutation, Ras85DV12, is analogous to oncogenic mutations found in human RAS proteins. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G12V in the fly Ras85D gene (corresponds to G12V in the human KRAS and HRAS genes).
The Scribble polarity complex plays a key role in determining cell polarity and cell proliferation in epithelial cells. Classical amorphic and hypomorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both scrib and l(2)gl.
Drosophila cancer models using Ras85DV12 and genes encoding components of the Scribble complex have been developed using epithelial systems. See 'cancer, epithelial, RAS-LLGL-related' (FBhh0000588) and 'cancer, epithelial, RAS-SCRIB-related' (FBhh0000585).
[updated May 2019 by FlyBase; FBrf0222196]
Ortholog of human SCRIB and LRRC1 (1 Drosophila to 2 human); Dmel\scrib shares 33% identity and 45% similarity with the human SCRIB gene. The human LRRC1 gene encodes a much smaller protein, corresponding to the amino end of SCRIB and Dmel\scrib; it shares 57% identity and 73% similarity with Dmel\scrib within that extent.