@article{8558453d14b040f8b79b055696c0243f,
title = "The CRL4 E3 ligase Mahjong/DCAF1 controls cell competition through the transcription factor Xrp1, independently of polarity genes",
abstract = "Cell competition, the elimination of cells surrounded by more fit neighbors, is proposed to suppress tumorigenesis. Mahjong (Mahj), a ubiquitin E3 ligase substrate receptor, has been thought to mediate competition of cells mutated for lethal giant larvae (lgl), a neoplastic tumor suppressor that defines apical-basal polarity of epithelial cells. Here, we show that Drosophila cells mutated for mahjong, but not for lgl [l(2)gl], are competed because they express the bZip-domain transcription factor Xrp1, already known to eliminate cells heterozygous for ribosomal protein gene mutations (Rp/+ cells). Xrp1 expression in mahj mutant cells results in activation of JNK signaling, autophagosome accumulation, eIF2α phosphorylation and lower translation, just as in Rp/+ cells. Cells mutated for damage DNA binding-protein 1 (ddb1; pic) or cullin 4 (cul4), which encode E3 ligase partners of Mahj, also display Xrp1-dependent phenotypes, as does knockdown of proteasome subunits. Our data suggest a new model of mahj-mediated cell competition that is independent of apical-basal polarity and couples Xrp1 to protein turnover.",
keywords = "Cell competition, Cullin 4, DCAF1, DDB1, Lethal giant larvae, Mahjong, Xrp1",
author = "Amit Kumar and Baker, {Nicholas E.}",
note = "Funding Information: This project was supported by the National Institutes of Health (GM104213). Deposited in PMC for release after 12 months. Funding Information: We thank Drs W.-M. Deng, C.-T. Chien, K. Irvine, D. Pan, J. Secombe and H. Wang for fly stocks. Other fly stocks were obtained from the Bloomington Drosophila Stock Center (supported by NIH P40OD018537) and the Vienna Drosophila Resource Center. We thank Drs A. Jenny, C. Khan, M. Kiparaki and S. Nair for comments on manuscript, Dr Kiparaki for sharing unpublished data, and Dr Khan for sharing unpublished fly stocks. Confocal microscopy was performed in the Analytical Imaging Facility of the Albert Einstein College of Medicine (supported by the NCI P30CA013330) using the Leica SP8 microscope acquired through NIH SIG 1S10 OD023591. The monoclonal antibody mAb40-1a developed by J. R. Sanes was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD and maintained at the University of Iowa, Department of Biology, Iowa City, IA 52242. This project was supported by the National Institutes of Health (GM104213). Deposited in PMC for release after 12 months. Funding Information: We thank Drs W.-M. Deng, C.-T. Chien, K. Irvine, D. Pan, J. Secombe and H. Wang for fly stocks. Other fly stocks were obtained from the Bloomington Drosophila Stock Center (supported by NIH P40OD018537) and the Vienna Drosophila Resource Center. We thank Drs A. Jenny, C. Khan, M. Kiparaki and S. Nair for comments on manuscript, Dr Kiparaki for sharing unpublished data, and Dr Khan for sharing unpublished fly stocks. Confocal microscopy was performed in the Analytical Imaging Facility of the Albert Einstein College of Medicine (supported by the NCI P30CA013330) using the Leica SP8 microscope acquired through NIH SIG 1S10 OD023591. The monoclonal antibody mAb40-1a developed by J. R. Sanes was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD and maintained at the University of Iowa, Department of Biology, Iowa City, IA 52242. Publisher Copyright: {\textcopyright} 2022. Published by The Company of Biologists Ltd.",
year = "2022",
month = nov,
doi = "10.1242/dev.200795",
language = "English (US)",
volume = "149",
journal = "Journal of Embryology and Experimental Morphology",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "22",
}