Abstract:
:The tumor suppressor BAP1 interacts with chromatin-associated proteins and regulates cell proliferation, but its mechanism of action and regulation remain poorly defined. We show that the ubiquitin-conjugating enzyme UBE2O multi-monoubiquitinates the nuclear localization signal of BAP1, thereby inducing its cytoplasmic sequestration. This activity is counteracted by BAP1 autodeubiquitination through intramolecular interactions. Significantly, we identified cancer-derived BAP1 mutations that abrogate autodeubiquitination and promote its cytoplasmic retention, indicating that BAP1 autodeubiquitination ensures tumor suppression. The antagonistic relationship between UBE2O and BAP1 is also observed during adipogenesis, whereby UBE2O promotes differentiation and cytoplasmic localization of BAP1. Finally, we established a putative targeting consensus sequence of UBE2O and identified numerous chromatin remodeling factors as potential targets, several of which tested positive for UBE2O-mediated ubiquitination. Thus, UBE2O defines an atypical ubiquitin-signaling pathway that coordinates the function of BAP1 and establishes a paradigm for regulation of nuclear trafficking of chromatin-associated proteins.
journal_name
Mol Celljournal_title
Molecular cellauthors
Mashtalir N,Daou S,Barbour H,Sen NN,Gagnon J,Hammond-Martel I,Dar HH,Therrien M,Affar el Bdoi
10.1016/j.molcel.2014.03.002subject
Has Abstractpub_date
2014-05-08 00:00:00pages
392-406issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(14)00207-Xjournal_volume
54pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract::MicroRNAs (miRNAs) play a pivotal role in the regulation of genes involved in diverse processes such as development, differentiation, and cellular growth control. Recently, many viral-encoded miRNAs have been discovered, for the most part in viruses transcribed from double-stranded DNA genomes. As with their cellular ...
journal_title:Molecular cell
pub_type: 杂志文章,评审
doi:10.1016/j.molcel.2005.09.012
更新日期:2005-10-07 00:00:00
abstract::Transcript-selective translational regulation of epithelial-mesenchymal transition (EMT) by transforming growth factor-β (TGF-β) is directed by the hnRNP E1-containing TGF-β-activated-translational (BAT) mRNP complex. Herein, eukaryotic elongation factor-1 A1 (eEF1A1) is identified as an integral component of the BAT ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2011.02.003
更新日期:2011-02-18 00:00:00
abstract::We have identified ARAP1 and ARAP2 and examined ARAP1 as a possible link between phosphoinositide-, Arf-, and Rho-mediated cell signaling. ARAP1 contains Arf GAP, Rho GAP, Ankyrin repeat, Ras-associating, and five PH domains. In vitro, ARAP1 had Rho GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent A...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(02)00428-8
更新日期:2002-01-01 00:00:00
abstract::The mechanisms controlling growth and patterning along the proximal-distal axis of the vertebrate limb are yet to be understood. We show that restriction of expression of the homeobox gene Meis2 to proximal regions of the limb bud is essential for limb development, since ectopic Meis2 severely disrupts limb outgrowth....
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80393-7
更新日期:1999-11-01 00:00:00
abstract::When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activi...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2018.04.027
更新日期:2018-06-21 00:00:00
abstract::RNA-mediated gene silencing in human cells requires the accurate generation of ∼22 nt microRNAs (miRNAs) from double-stranded RNA substrates by the endonuclease Dicer. Although the phylogenetically conserved RNA-binding proteins TRBP and PACT are known to contribute to this process, their mode of Dicer binding and the...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2014.11.030
更新日期:2015-02-05 00:00:00
abstract::In this issue of Molecular Cell, Weinert et al. (2013) demonstrate that the intermediary metabolite acetyl-phosphate is an important acetyl donor that contributes to global protein acetylation in growth-arrested E. coli. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2013.07.006
更新日期:2013-07-25 00:00:00
abstract::CRISPR-Cas immunity requires integration of short, foreign DNA fragments into the host genome at the CRISPR locus, a site consisting of alternating repeat sequences and foreign-derived spacers. In most CRISPR systems, the proteins Cas1 and Cas2 form the integration complex and are both essential for DNA acquisition. M...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2018.12.015
更新日期:2019-02-21 00:00:00
abstract::Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes mellitus. To elucidate the molecular function of a mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules are bound to the promoter. Each...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(02)00704-9
更新日期:2002-11-01 00:00:00
abstract::Macroautophagy (autophagy) is a lysosome-dependent degradation process that has been implicated in age-associated diseases. Autophagy is involved in both cell survival and cell death, but little is known about the mechanisms that distinguish its use during these distinct cell fates. Here, we identify the microRNA miR-...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2014.09.011
更新日期:2014-11-06 00:00:00
abstract::Caspase-7 is an obligate dimer of catalytic domains, with generation of activity requiring limited proteolysis within a region that separates the large and small chains of each domain. Using hybrid dimers we distinguish the relative contribution of each domain to catalysis by the whole molecule. We demonstrate that th...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2006.06.020
更新日期:2006-08-01 00:00:00
abstract::K-Ras associates with the plasma membrane (PM) through farnesylation that functions in conjunction with an adjacent polybasic sequence. We show that phosphorylation by protein kinase C (PKC) of S181 within the polybasic region promotes rapid dissociation of K-Ras from the PM and association with intracellular membrane...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2006.01.012
更新日期:2006-02-17 00:00:00
abstract::In a recent publication in Science, Kujirai et al. (2018) use single-particle cryo-EM to resolve several Pol II-nucleosome interactions, shedding new light on transcription elongation in a native chromatin environment. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2018.11.027
更新日期:2018-12-06 00:00:00
abstract::PRDM16 is a transcription co-factor that plays critical roles in development of brown adipose tissue, as well as maintenance of adult hematopoietic and neural stem cells. Here we report that PRDM16 is a histone H3K4 methyltransferase on chromatin. Mutation in the N-terminal PR domain of PRDM16 abolishes the intrinsic ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2016.03.010
更新日期:2016-04-21 00:00:00
abstract::AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2008.03.003
更新日期:2008-04-25 00:00:00
abstract::In this issue of Molecular Cell, Miotto and Struhl (2010) suggest that replication licensing, the loading of Mcm2-7 onto DNA, is promoted by HBO1 acetylating histone H4 at replication origins, providing a molecular view of how chromatin status influences origin usage. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2009.12.028
更新日期:2010-01-15 00:00:00
abstract::Stress granules and P-bodies are cytosolic biomolecular condensates that dynamically form by the phase separation of RNAs and proteins. They participate in translational control and buffer the proteome. Upon stress, global translation halts and mRNAs bound to the translational machinery and other proteins coalesce to ...
journal_title:Molecular cell
pub_type: 杂志文章,评审
doi:10.1016/j.molcel.2019.09.014
更新日期:2019-10-17 00:00:00
abstract::The selective degradation of intracellular components by autophagy involves sequential interactions of the cargo with a receptor, which also binds the autophagosomal protein Atg8 and a scaffold protein. Here, we demonstrated that mutations in C. elegans epg-11, which encodes an arginine methyltransferase homologous to...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2013.09.014
更新日期:2013-11-07 00:00:00
abstract::In this study, we used Saccharomyces cerevisiae to identify a biological network that prevents the deleterious effects of endogenous reactive oxygen species. The absence of Tsa1, a key peroxiredoxin, caused increased rates of mutations, chromosomal rearrangements, and recombination. Defects in recombinational DNA doub...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2005.02.008
更新日期:2005-03-04 00:00:00
abstract::Certain nascent peptide sequences, when within the ribosomal exit tunnel, can inhibit translation termination and/or peptide elongation. The 24 residue leader peptidyl-tRNA of the tna operon of E. coli, TnaC-tRNA(Pro), in the presence of excess tryptophan, resists cleavage at the tnaC stop codon. TnaC residue Trp12 is...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2005.06.013
更新日期:2005-08-05 00:00:00
abstract::Allosteric communication between interacting molecules is fundamental to signal transduction and many other cellular processes. To better understand the relationship between nuclear receptor (NR) ligand positioning and the formation of the coactivator binding pocket, we investigated the determinants of ligand selectiv...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(04)00054-1
更新日期:2004-02-13 00:00:00
abstract::Productive splicing of human precursor messenger RNAs (pre-mRNAs) requires the correct selection of authentic splice sites (SS) from the large pool of potential SS. Although SS consensus sequence and splicing regulatory proteins are known to influence SS usage, the mechanisms ensuring the effective suppression of cryp...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2018.08.030
更新日期:2018-11-01 00:00:00
abstract::B and T cell receptor gene assembly by V(D)J recombination is tightly regulated during lymphoid development. The mechanisms involved in this regulation are poorly understood. Here we show that nucleosomal DNA is refractory to V(D)J cleavage. However, the presence of HMG1, a chromatin-associated nonhistone DNA-binding ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80297-x
更新日期:1998-12-01 00:00:00
abstract::EGFR activates phosphatidylinositide 3-kinase (PI3K), but the mechanism underlying this activation is not completely understood. We demonstrated here that EGFR activation resulted in lysine acetyltransferase 5 (KAT5)-mediated K395 acetylation of the platelet isoform of phosphofructokinase 1 (PFKP) and subsequent trans...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2018.03.018
更新日期:2018-04-19 00:00:00
abstract::The oncogenic process often leads to a loss of normal telomere length control, usually as a result of activation of telomerase. Nevertheless, there are also telomerase-independent events that involve a Rad50-dependent recombination mechanism to maintain telomere length. Previous work has implicated the Rb family of pr...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2006.02.016
更新日期:2006-04-07 00:00:00
abstract::R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome instability and regulated gene expression. To enable precision analysis of R-loops in vivo, we develop an RNase-H-based approach; this reveals predominant R-loop formation near gene promoters with strong G/C skew and propensity to form G-qua...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2017.10.008
更新日期:2017-11-16 00:00:00
abstract::We report the identification of histone PARylation factor 1 (HPF1; also known as C4orf27) as a regulator of ADP-ribosylation signaling in the DNA damage response. HPF1/C4orf27 forms a robust protein complex with PARP-1 in cells and is recruited to DNA lesions in a PARP-1-dependent manner, but independently of PARP-1 c...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2016.03.008
更新日期:2016-05-05 00:00:00
abstract::Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. In the licensing step of DNA replication, CDT-1 is loaded onto chromatin to subsequently promote the recruitment of additional replication factors, including CDC-45 and GINS. During the elongation step, th...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2011.08.028
更新日期:2011-10-07 00:00:00
abstract::Eukaryotic gene expression regulation involves thousands of distal regulatory elements. Understanding the quantitative contribution of individual enhancers to gene expression is critical for assessing the role of disease-associated genetic risk variants. Yet, we lack the ability to accurately link genes with their dis...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2020.09.005
更新日期:2020-10-15 00:00:00
abstract::Pilin assembly into type IV pili is required for virulence by bacterial pathogens that cause diseases such as cholera, pneumonia, gonorrhea, and meningitis. Crystal structures of soluble, N-terminally truncated pilin from Vibrio cholera toxin-coregulated pilus (TCP) and full-length PAK pilin from Pseudomonas aeruginos...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(03)00170-9
更新日期:2003-05-01 00:00:00