@article{a81dfbc7c2d545cb8c8e960e5db4a829,
title = "The CUL4-DDB1 ubiquitin ligase complex controls adult and embryonic stem cell differentiation and homeostasis",
abstract = "Little is known on post-transcriptional regulation of adult and embryonic stem cell maintenance and differentiation. Here we characterize the role of Ddb1, a component of the CUL4- DDB1 ubiquitin ligase complex. Ddb1 is highly expressed in multipotent hematopoietic progenitors and its deletion leads to abrogation of both adult and fetal hematopoiesis, targeting specifically transiently amplifying progenitor subsets. However, Ddb1 deletion in non-dividing lymphocytes has no discernible phenotypes. Ddb1 silencing activates Trp53 pathway and leads to significant effects on cell cycle progression and rapid apoptosis. The abrogation of hematopoietic progenitor cells can be partially rescued by simultaneous deletion of Trp53. Conversely, depletion of DDB1 in embryonic stem cell (ESC) leads to differentiation albeit negative effects on cell cycle and apoptosis. Mass spectrometry reveals differing protein interactions between DDB1 and distinct DCAFs, the substrate recognizing components of the E3 complex, between cell types. Our studies identify CUL4-DDB1 complex as a novel post-translational regulator of stem and progenitor maintenance and differentiation.",
author = "Jie Gao and Buckley, {Shannon M.} and Luisa Cimmino and Maria Guillamot and Alexandros Strikoudis and Yong Cang and Goff, {Stephen P.} and Iannis Aifantis",
note = "Funding Information: We would like to thank the NYU Genome Technology Center (supported in part by NIH/NCI P30 CA016087-30 grant) for expert assistance with micro-array experiments, and the NYU Flow Cytometry facility (supported in part by NIH/NCI 5 P30CA16087-31) for expert cell sorting, the NYU Histology Core (5P30CA16087-31), and the Transgenic Mouse Core (NYU Cancer Institute Center Grant (5P30CA16087-31). We would also like to thank Dr H Li and Dr T Liu at the Center for Advanced Proteomics Research, Rutgers New Jersey School of Medicine, and Dr B Ueberheide at the NYU School of Medicine Proteomics Resource Center supported by the Cancer Center Support Grant, P30CA016087 for selected mass spectrometry analysis. IA is supported by the National Institutes of Health (RO1CA133379, RO1CA105129, R21CA141399, RO1CA149655, and RO1GM088847), NYS Department of Health NY STEM (C028130), the Leukemia & Lymphoma Society (TRP grant), the V Foundation for Cancer Research, the Irma T. Hirschl Trust, and the Dana Foundation. JG was supported by the Lady Tata Memorial Trust and Molecular Oncology and Immunology training grant, and SMB was supported by the Helen L and Martin S Kimmel Stem Cell Postdoctoral fellowship and the NIH institutional training grant (1T32CA160002-01). Publisher Copyright: {\textcopyright} Gao et al.",
year = "2015",
month = nov,
day = "27",
doi = "10.7554/eLife.07539",
language = "English (US)",
volume = "4",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "NOVEMBER2015",
}