Knockdown of PR-DUB subunit in the developing eye and wing results in mis-patterned tissues with altered size and shape.

Unlabelled: The deubiquitinating enzyme BAP1, the catalytic subunit of the PR-DUB complex, is implicated in several cancers, in the familial cancer syndrome BAP1 Tumor Predisposition Syndrome, and in the neurodevelopmental disorder Küry -Isidor syndrome. In there are numerous reports in the literature describing developmental patterning phenotypes for several chromatin regulators including the discovery of Polycomb itself, but corresponding adult morphological phenotypes caused by developmental dysregulation of ortholog ( ) are less well-described. We report here that knockdown of in the eye and wing produce concomitant chromatin dysregulation phenotypes.

Rabex-5 E3 and Rab5 GEF domains differ in their regulation of Ras, Notch, and PI3K signaling in Drosophila wing development.

Rabex-5 (also called RabGEF1), a protein originally characterized for its Rab5 GEF function, also has an A20-like E3 ubiquitin ligase domain. We and others reported that Rabex-5 E3 activity promotes Ras mono- and di-ubiquitination to inhibit Ras signaling in Drosophila and mammals. Subsequently, we reported that Rabex-5 inhibits Notch signaling in the Drosophila hematopoietic system.

Characterization of Ras Y4H mutants in .

Ras signaling plays a highly conserved role from flies to mammals in establishing proper development, and its dysregulation can lead to cancer. In , we demonstrated that Ras Tyrosine 4 (Y4) was required for inhibitory ubiquitination by Rabex-5. In humans, rare histidine substitution mutations at Y4 are found in HRas in cerebellar glioblastomas (cGBMs).

Lysines K117 and K147 play conserved roles in Ras activation from Drosophila to mammals.

Ras signaling plays an important role in growth, proliferation, and developmental patterning. Maintaining appropriate levels of Ras signaling is important to establish patterning in development and to prevent diseases such as cancer in mature organisms. The Ras protein is represented by Ras85D in Drosophila and by HRas, NRas, and KRas in mammals.