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We reported that Cullin4B-Ring E3 ligase complex (CRL4B) is physically associated with Polycomb-repressive complex 2 (PRC2). We showed that CRL4B possesses an intrinsic transcription repressive activity by promoting H2AK119 monoubiquitination. Ablation of Cul4b or depletion of CUL4B, the main component of CRL4B, resulted in loss of not only H2AK119(More)
CUL4B, a scaffold protein that assembles the CRL4B ubiquitin ligase complex, participates in the regulation of a broad spectrum of biological processes. Here, we demonstrate a crucial role of CUL4B in driving cell cycle progression. We show that loss of CUL4B results in a significant reduction in cell proliferation and causes G1 cell cycle arrest,(More)
Activation of Wnt/β-catenin signalling is frequently observed in many types of cancer including hepatocellular carcinoma (HCC). We recently reported that cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, is overexpressed in many types of solid tumours and contributes to epigenetic silencing of tumour suppressors. In this(More)
Cullin-RING ubiquitin ligases (CRLs) participate in the regulation of diverse cellular processes including cell cycle progression. Mutations in the X-linked CUL4B, a member of the cullin family, cause mental retardation and other developmental abnormalities in humans. Cells that are deficient in CUL4B are severely selected against in vivo in heterozygotes.(More)
Chlorambucil (CLB) is an alkylating agent commonly used in the treatment of several neoplastic disorders. The mechanisms underlying resistance to this drug are not fully defined. We used the DNA alkaline elution technique to study cross-link formation in the wild type (K1) and a CLB-resistant (ChlR) Chinese hamster ovary cell line. [14C]CLB was used to(More)
Cullin-RING ligases (CRLs) complexes participate in the regulation of diverse cellular processes, including cell cycle progression, transcription, signal transduction and development. Serving as the scaffold protein, cullins are crucial for the assembly of ligase complexes, which recognize and target various substrates for proteosomal degradation. Mutations(More)
Imitation Switch (ISWI) is a member of the SWI2/SNF2 superfamily of ATP-dependent chromatin remodelers, which are involved in multiple nuclear functions, including transcriptional regulation, replication, and chromatin assembly. Mammalian genomes encode two ISWI orthologs, SNF2H and SNF2L. In order to clarify the molecular mechanisms governing the(More)
Cullin 4B (CUL4B) is a component of the Cullin 4B-Ring E3 ligase (CRL4B) complex that functions in proteolysis and in epigenetic regulation. CUL4B possesses tumor-promoting properties and is markedly upregulated in many types of human cancers. To determine the role of CUL4B in liver tumorigenesis, we generated transgenic mice that expressed human CUL4B in(More)
Cullin 4B (CUL4B) is a scaffold protein involved in the assembly of cullin-RING ubiquitin ligase (E3) complexes. Contemporary reports have identified multiple mutations of CUL4B gene as being causally associated with X-linked intellectual disability (XLID). Identifying the specific protein substrates will help to better understand the physiological(More)
Cancer progression requires a permissive microenvironment that shields cancer from the host immunosurveillance. The presence of myeloid-derived suppressor cells (MDSC) is a key feature of a tumor-permissive microenvironment. Cullin 4B (CUL4B), a scaffold protein in the Cullin 4B-RING E3 ligase complex (CRL4B), represses tumor suppressors through diverse(More)