scholarly journals Polyubiquitylation of Histone H2B

2008 ◽  
Vol 19 (9) ◽  
pp. 3616-3624 ◽  
Author(s):  
Fuqiang Geng ◽  
William P. Tansey
Keyword(s):  
Ubiquitin Ligase ◽  
Biological Effects ◽  
Covalent Modification ◽  
Epigenetic Mark ◽  
Histone H2b ◽  
Silent Genes ◽  
Lysine Residues ◽  
Histone Ubiquitylation ◽  
In Trans ◽  
Ubiquitin Moiety

Covalent modification of histones by ubiquitylation is a prominent epigenetic mark that features in a variety of chromatin-based events such as histone methylation, gene silencing, and repair of DNA damage. The prototypical example of histone ubiquitylation is that of histone H2B in Saccharomyces cerevisiae. In this case, attachment of ubiquitin to lysine 123 (K123) of H2B is important for regulation of both active and transcriptionally silent genes and participates in trans to signal methylation of histone H3. It is generally assumed that H2B is monoubiquitylated at K123 and that it is this single ubiquitin moiety that influences H2B function. To determine whether this assumption is correct, we have re-examined the ubiquitylation status of endogenous H2B in yeast. We find that, contrary to expectations, H2B is extensively polyubiquitylated. Polyubiquitylation of H2B appears to occur within the context of chromatin and is not associated with H2B destruction. There are at least two distinct modes of H2B polyubiquitylation: one that occurs at K123 and depends on the Rad6–Bre1 ubiquitylation machinery and another that occurs on multiple lysine residues and is catalyzed by an uncharacterized ubiquitin ligase(s). Interestingly, these ubiquitylation events are under the influence of different combinations of ubiquitin-specific proteases, suggesting that they have distinct biological functions. These results raise the possibility that some of the biological effects of ubiquitylation of H2B are exerted via ubiquitin chains, rather than a single ubiquitin group.

scholarly journals Characterization of Multiple Multivesicular Body Sorting Determinants within Sna3: A Role for the Ubiquitin Ligase Rsp5

2007 ◽  
Vol 18 (2) ◽  
pp. 707-720 ◽  
Author(s):  
Andrea J. Oestreich ◽  
Mariam Aboian ◽  
Jacqueline Lee ◽  
Ishara Azmi ◽  
Johanna Payne ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Multivesicular Body ◽  
Covalent Modification ◽  
Cellular Functions ◽  
Ww Domains ◽  
Amino Terminal ◽  
Viral Budding ◽  
Lysine Residues ◽  
Lysosome Related Organelles ◽  
Critical Regions

A subset of proteins that transit the endosomal system are directed into the intralumenal vesicles of multivesicular bodies (MVBs). MVB formation is critical for a variety of cellular functions including receptor down-regulation, viral budding, antigen presentation, and the generation of lysosome-related organelles. Entry of transmembrane proteins into the intralumenal vesicles of a MVB is a highly regulated process that is positively modulated by covalent modification of cargoes with ubiquitin. To identify additional MVB sorting signals, we examined the previously described ubiquitination-independent MVB cargo Sna3. Although Sna3 ubiquitination is not essential, Sna3 MVB sorting is positively modulated by its ubiquitination. Examination of MVB sorting determinants within a form of Sna3 lacking all lysine residues identified two critical regions: an amino-terminal tyrosine-containing region and a carboxyl-terminal PPAY motif. This PPAY motif interacts with the WW domains of the ubiquitin ligase Rsp5, and mutations in either the WW or, surprisingly, the HECT domains of Rsp5 negatively impacted MVB targeting of lysine-minus Sna3. These data indicate that Rsp5 function is required for MVB targeting of Sna3 in a capacity beyond cargo ubiquitination. These results uncover a series of determinants impacting Sna3 MVB sorting, including unexpected roles for Rsp5.

scholarly journals The CRL4Cdt2 Ubiquitin Ligase Mediates the Proteolysis of Cyclin-Dependent Kinase Inhibitor Xic1 through a Direct Association with PCNA

2010 ◽  
Vol 30 (17) ◽  
pp. 4120-4133 ◽  
Author(s):  
Dong Hyun Kim ◽  
Varija N. Budhavarapu ◽  
Carlos R. Herrera ◽  
Hyung Wook Nam ◽  
Yu Sam Kim ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Proliferating Cell Nuclear Antigen ◽  
Kinase Inhibitor ◽  
Binding Domain ◽  
Nuclear Antigen ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Terminal Domain ◽  
Lysine Residues ◽  
Proliferating Cell

ABSTRACT During DNA polymerase switching, the Xenopus laevis Cip/Kip-type cyclin-dependent kinase inhibitor Xic1 associates with trimeric proliferating cell nuclear antigen (PCNA) and is recruited to chromatin, where it is ubiquitinated and degraded. In this study, we show that the predominant E3 for Xic1 in the egg is the Cul4-DDB1-XCdt2 (Xenopus Cdt2) (CRL4Cdt2) ubiquitin ligase. The addition of full-length XCdt2 to the Xenopus extract promotes Xic1 turnover, while the N-terminal domain of XCdt2 (residues 1 to 400) cannot promote Xic1 turnover, despite its ability to bind both Xic1 and DDB1. Further analysis demonstrated that XCdt2 binds directly to PCNA through its C-terminal domain (residues 401 to 710), indicating that this interaction is important for promoting Xic1 turnover. We also identify the cis-acting sequences required for Xic1 binding to Cdt2. Xic1 binds to Cdt2 through two domains (residues 161 to 170 and 179 to 190) directly flanking the Xic1 PCNA binding domain (PIP box) but does not require PIP box sequences (residues 171 to 178). Similarly, human p21 binds to human Cdt2 through residues 156 to 161, adjacent to the p21 PIP box. In addition, we identify five lysine residues (K180, K182, K183, K188, and K193) immediately downstream of the Xic1 PIP box and within the second Cdt2 binding domain as critical sites for Xic1 ubiquitination. Our studies suggest a model in which both the CRL4Cdt2 E3- and PIP box-containing substrates, like Xic1, are recruited to chromatin through independent direct associations with PCNA.

Resveratrol activates the histone H2B ubiquitin ligase, RNF20, in MDA-MB-231 breast cancer cells

2013 ◽  
Vol 5 (2) ◽  
pp. 790-800 ◽  
Author(s):  
Chia-Yeh Lin ◽  
Wei-Chun Hsiao ◽  
Duncan Edward Wright ◽  
Chia-Ling Hsu ◽  
Yi-Chen Lo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
Breast Cancer Cells ◽  
Histone H2b

scholarly journals Bigram-PGK: phosphoglycerylation prediction using the technique of bigram probabilities of position specific scoring matrix

2019 ◽  
Vol 20 (S2) ◽  
Author(s):  
Abel Chandra ◽  
Alok Sharma ◽  
Abdollah Dehzangi ◽  
Daichi Shigemizu ◽  
Tatsuhiko Tsunoda
Keyword(s):  
Amino Acids ◽  
Cell Biology ◽  
Covalent Modification ◽  
Evolutionary Information ◽  
Support Vector ◽  
Computational Techniques ◽  
Post Translational Modification ◽  
Statistical Measures ◽  
Scoring Matrices ◽  
Lysine Residues

Abstract Background The biological process known as post-translational modification (PTM) is a condition whereby proteomes are modified that affects normal cell biology, and hence the pathogenesis. A number of PTMs have been discovered in the recent years and lysine phosphoglycerylation is one of the fairly recent developments. Even with a large number of proteins being sequenced in the post-genomic era, the identification of phosphoglycerylation remains a big challenge due to factors such as cost, time consumption and inefficiency involved in the experimental efforts. To overcome this issue, computational techniques have emerged to accurately identify phosphoglycerylated lysine residues. However, the computational techniques proposed so far hold limitations to correctly predict this covalent modification. Results We propose a new predictor in this paper called Bigram-PGK which uses evolutionary information of amino acids to try and predict phosphoglycerylated sites. The benchmark dataset which contains experimentally labelled sites is employed for this purpose and profile bigram occurrences is calculated from position specific scoring matrices of amino acids in the protein sequences. The statistical measures of this work, such as sensitivity, specificity, precision, accuracy, Mathews correlation coefficient and area under ROC curve have been reported to be 0.9642, 0.8973, 0.8253, 0.9193, 0.8330, 0.9306, respectively. Conclusions The proposed predictor, based on the feature of evolutionary information and support vector machine classifier, has shown great potential to effectively predict phosphoglycerylated and non-phosphoglycerylated lysine residues when compared against the existing predictors. The data and software of this work can be acquired from https://github.com/abelavit/Bigram-PGK.

scholarly journals Bre1a, a Histone H2B Ubiquitin Ligase, Regulates the Cell Cycle and Differentiation of Neural Precursor Cells

2014 ◽  
Vol 34 (8) ◽  
pp. 3067-3078 ◽  
Author(s):  
Y. Ishino ◽  
Y. Hayashi ◽  
M. Naruse ◽  
K. Tomita ◽  
M. Sanbo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Histone H2b

scholarly journals The plasma membrane Ca2+ pump mutant lysine591 → arginine retains some activity, but is still inactivated by fluorescein isothiocyanate

1996 ◽  
Vol 317 (1) ◽  
pp. 41-44 ◽  
Author(s):  
Hugo P. ADAMO ◽  
Adelaida G. FILOTEO ◽  
John T. PENNISTON
Keyword(s):  
Enzyme Activity ◽  
Plasma Membrane ◽  
Human Plasma ◽  
Fluorescein Isothiocyanate ◽  
Covalent Modification ◽  
Transport Activity ◽  
Wild Type ◽  
Pump Function ◽  
Irreversible Inhibition ◽  
Lysine Residues

Inactivation of the wild-type human plasma membrane Ca2+ pump (isoform 4b) by fluorescein isothiocyanate is accompanied by covalent modification of Lys591. The mutation of Lys591 to arginine reduced the Ca2+ transport activity to 35% of the wild-type, and diminished the amount of acylphosphate formed from ATP by a corresponding amount. When this mutant was treated with fluorescein isothiocyanate, the enzyme was still irreversibly inactivated, even though no reactive residue was available at position 591. The results show that, although Ca2+ pump function is sensitive to the residue at position 591, Lys591 is not essential for enzyme activity. They also demonstrate that irreversible inhibition of the plasma membrane Ca2+ pump by fluorescein isothiocyanate does not require the covalent modification of Lys591. This indicates that fluorescein isothiocyanate reacts with lysine residues at other positions in addition to Lys591.

scholarly journals Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Li Zhang ◽  
Prashant Rajbhandari ◽  
Christina Priest ◽  
Jaspreet Sandhu ◽  
Xiaohui Wu ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Plasma Cholesterol ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Homeostasis ◽  
High Cholesterol Diet ◽  
High Cholesterol ◽  
Cholesterol Levels ◽  
Expression Of Genes ◽  
Lysine Residues ◽  
Genetic Deletion

Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show that RNF145 triggers ubiquitination of SCAP on lysine residues within a cytoplasmic loop essential for COPII binding, potentially inhibiting its transport to Golgi and subsequent processing of SREBP-2. These findings define an additional mechanism linking hepatic sterol levels to the reciprocal actions of the SREBP-2 and LXR pathways.

scholarly journals Hepatitis B Virus Replication and Release Are Independent of Core Lysine Ubiquitination

2009 ◽  
Vol 83 (10) ◽  
pp. 4923-4933 ◽  
Author(s):  
Mayra L. Garcia ◽  
Rushelle Byfield ◽  
Michael D. Robek
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Ubiquitin Ligase ◽  
Core Protein ◽  
Structural Proteins ◽  
Hbv Replication ◽  
Virion Release ◽  
B Virus ◽  
Lysine Residues ◽  
Ubiquitin Conjugation

ABSTRACT Ubiquitin conjugation to lysine residues regulates a variety of protein functions, including endosomal trafficking and degradation. While ubiquitin plays an important role in the release of many viruses, the requirement for direct ubiquitin conjugation to viral structural proteins is less well understood. Some viral structural proteins require ubiquitin ligase activity, but not ubiquitin conjugation, for efficient release. Recent evidence has shown that, like other viruses, hepatitis B virus (HBV) requires a ubiquitin ligase for release from the infected cell. The HBV core protein contains two lysine residues (K7 and K96), and K96 has been suggested to function as a potential ubiquitin acceptor site based on the fact that previous studies have shown that mutation of this amino acid to alanine blocks HBV release. We therefore reexamined the potential connection between core lysine ubiquitination and HBV replication, protein trafficking, and virion release. In contrast to alanine substitution, we found that mutation of K96 to arginine, which compared to alanine is more conserved but also cannot mediate ubiquitin conjugation, does not affect either virus replication or virion release. We also found that the core lysine mutants display wild-type sensitivity to the antiviral activity of interferon, which demonstrates that ubiquitination of core lysines does not mediate the interferon-induced disruption of HBV capsids. However, mutation of K96 to arginine alters the nuclear-cytoplasmic distribution of core, leading to an accumulation in the nucleolus. In summary, these studies demonstrate that although ubiquitin may regulate the HBV replication cycle, these mechanisms function independently of direct lysine ubiquitination of core protein.

scholarly journals Histone H2B ubiquitylation and H3 lysine 4 methylation prevent ectopic silencing of euchromatic loci important for the cellular response to heat

2011 ◽  
Vol 22 (15) ◽  
pp. 2741-2753 ◽  
Author(s):  
Amy Leung ◽  
Ivelisse Cajigas ◽  
Peilin Jia ◽  
Elena Ezhkova ◽  
Jason H. Brickner ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cellular Response ◽  
Cell Wall Integrity ◽  
Silent Chromatin ◽  
Comparative Transcriptome ◽  
H3k4 Methylation ◽  
Histone H2b ◽  
Lysine Residues ◽  
Dna Adenine Methyltransferase ◽  
Active Genes

In Saccharomyces cerevisiae, ubiquitylation of histone H2B signals methylation of histone H3 at lysine residues 4 (K4) and 79. These modifications occur at active genes but are believed to stabilize silent chromatin by limiting movement of silencing proteins away from heterochromatin domains. In the course of studying atypical phenotypes associated with loss of H2B ubiquitylation/H3K4 methylation, we discovered that these modifications are also required for cell wall integrity at high temperatures. We identified the silencing protein Sir4 as a dosage suppressor of loss of H2B ubiquitylation, and we showed that elevated Sir4 expression suppresses cell wall integrity defects by inhibiting the function of the Sir silencing complex. Using comparative transcriptome analysis, we identified a set of euchromatic genes—enriched in those required for the cellular response to heat—whose expression is attenuated by loss of H2B ubiquitylation but restored by disruption of Sir function. Finally, using DNA adenine methyltransferase identification, we found that Sir3 and Sir4 associate with genes that are silenced in the absence of H3K4 methylation. Our data reveal that H2B ubiquitylation/H3K4 methylation play an important role in limiting ectopic association of silencing proteins with euchromatic genes important for cell wall integrity and the response to heat.

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