Ubiquitin regulates a myriad of important cellular processes through covalent attachment to its substrates. A classic role for ubiquitin is to flag proteins for destruction by the proteasome. Recent studies indicate that ubiquitin-binding proteins (e.g. Rad23, Dsk2, Rpn10) play a pivotal role in transferring ubiquitylated proteins to the proteasome. However, the specific role of these ubiquitin receptors remains poorly defined. A key to unraveling the functions of these ubiquitin receptors is to identify their cellular substrates and biological circuits they are involved in. Although many strategies have been developed for substrate isolation, the identification of physiological targets of proteolytic pathways has proven to be quite challenging. Using a genome-wide functional screen, we have identified 11 yeast genes that cause slower growth upon their overexpression in cells lacking two ubiquitin-binding proteins Rad23 and Dsk2. Our results suggest that proper functioning of Rad23 and Dsk2 is required
TY - JOUR. T1 - Mechanism-based proteomics tools based on ubiquitin and ubiquitin-like proteins. T2 - Synthesis of active site-directed probes. AU - Ovaa, Huib. AU - Galardy, Paul J.. AU - Ploegh, Hidde L.. PY - 2005. Y1 - 2005. N2 - The families of ubiquitin and ubiquitin-like modifiers are involved in the regulation of many biochemical pathways. The steady-state level of polypeptide modification with these molecules depends on the opposing activity of conjugating and deconjugating enzymes. Here we describe the generation of mechanism-dependent active site-directed probes that target the large family of ubiquitin/ubiquitin-like isopeptidases. To maintain substrate specificity for these enzymes, we have based the development of these probes on full-length sequences of ubiquitin and several ubiquitin-like molecules. For their construction, this approach necessitates the use of a combination of organic synthesis and expressed protein ligation. These probes have been used in the isolation and ...
Linear ubiquitin chains are important regulators of cellular signalling pathways that control innate immunity and inflammation through nuclear factor (NF)-κB activation and protection against tumour necrosis factor-α-induced apoptosis. They are synthesized by HOIP, which belongs to the RBR (RING-bet …
ubiquitin a peptide 76 amino acids in length that can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains. Only the 76 amino acids of monoubiquitin product are shown in this entry. At the protein level, it is not possible to determine which of the four genes a given ubiquitin chain was derived from. Hundreds of ubiquitin ligases and hydrolases have been identified, implicating ubiquitin as a major regulatory element in many crucial cellular systems. It can be covalently bound to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer ...
We have probed the interactions between HOIP and NEMO by solving a cocrystal structure of NZF1 of human HOIP and CoZi of mouse NEMO, while our mutational studies have been performed using mouse HOIP. However, the surface residues from HOIP that interact with NEMO are fully conserved in human and mouse species (Fig. 3J). Our mutational analyses based on the structure of the cocrystal show that direct recognition of NEMO by HOIP plays a major role in NF-κB activation following conjugation of linear chains to NEMO. Although the RING-IBR-RING region of HOIP is the catalytic center for linear polyubiquitination by LUBAC (7), recent results obtained using an in vitro ubiquitin assay have suggested that the RING2 domain of HOIL-1L plays a role in linear polyubiquitination of NEMO (38). However, given that the HOIP-SHARPIN complex effectively linearly polyubiquitinates NEMO in vitro and activates NF-κB in cells (12), any involvement of the RING2 domain of HOIL-1L in linear polyubiquitination of NEMO ...
TY - JOUR. T1 - Vps9p CUE domain ubiquitin binding is required for efficient endocytic protein traffic. AU - Davies, Brian A.. AU - Topp, Justin D.. AU - Sfeir, Agnel J.. AU - Katzmann, David J.. AU - Carney, Darren S.. AU - Tall, Gregory G.. AU - Friedberg, Andrew S.. AU - Deng, Li. AU - Chen, Zhijian. AU - Horazdovsky, Bruce F.. PY - 2003/5/30. Y1 - 2003/5/30. N2 - Rab5 GTPases are key regulators of protein trafficking through the early stages of the endocytic pathway. The yeast Rab5 ortholog Vps21p is activated by its guanine nucleotide exchange factor Vps9p. Here we show that Vps9p binds ubiquitin and that the CUE domain is necessary and sufficient for this interaction. Vps9p ubiquitin binding is required for efficient endocytosis of Ste3p but not for the delivery of the biosynthetic cargo carboxypeptidase Y to the vacuole. In addition, Vps9p is itself monoubiquitylated. Ubiquitylation is dependent on a functional CUE domain and Rsp5p, an E3 ligase that participates in cell surface receptor ...
TY - JOUR. T1 - Hect E3 ubiquitin ligase Tom1 controls Dia2 degradation during the cell cycle. AU - Kim, Dong Hwan. AU - Koepp, Deanna M.. PY - 2012/11/1. Y1 - 2012/11/1. N2 - The ubiquitin proteasome system plays a pivotal role in controlling the cell cycle. The budding yeast F-box protein Dia2 is required for genomic stability and is targeted for ubiquitin-dependent degradation in a cell cycle-dependent manner, but the identity of the ubiquitination pathway is unknown. We demonstrate that the Hect domain E3 ubiquitin ligase Tom1 is required for Dia2 protein degradation. Deletion of DIA2 partially suppresses the temperature-sensitive phenotype of tom1 mutants. Tom1 is required for Dia2 ubiquitination and degradation during G1 and G2/M phases of the cell cycle, whereas the Dia2 protein is stabilized during S phase. We find that Tom1 binding to Dia2 is enhanced in G1 and reduced in S phase, suggesting a mechanism for this proteolytic switch. Tom1 recognizes specific, positively charged residues ...
Eukaryotes contain a highly conserved multienzyme system which covalently links a small protein, ubiquitin, to a variety of intracellular proteins that bear degradation signals recognized by this system. The resulting ubiquitin-protein conjugates are degraded by the 26S proteasome, an ATP-dependent protease. Pathways that involve ubiquitin play major roles in a huge variety of processes, including cell differentiation, cell cycle, and responses to stress. In this article we briefly review the design of the ubiquitin system, and describe two recent advances, the finding that ubiquitin ligases interact with specific components of the 26S proteasome, and the demonstration that peptides accelerate their uptake into cells by activating the N-end rule pathway, one of several proteolytic pathways of the ubiquitin system.. ...
Our work has revealed a partial molecular understanding for how BRCA1 recognizes DNA damage and competes with opposing DNA repair proteins to control genome integrity. We have demonstrated that an interaction between the BRCA1 BRCT domain and the RAP80 ubiquitin binding protein targets BRCA1 to K63-linked ubiquitin structures present at DNA damage sites. The RAP80 ubiquitin interaction motifs (UIMs) provide an ubiquitin recognition element to target the BRCA1 E3 ligase and a K63-ubiquitin specific deubiquitinating enzyme BRCC36 to DNA double strand breaks. Each of these activities is required for appropriate DNA damage checkpoint and repair responses (Sobhian et al. Science 2007; Shao et al. Genes&Dev 2009; Tang et al. Nat Struct & Mol Biol 2013; Jiang et al. Genes Dev 2015; Zeqiraj et al. Mol Cell 2015). Cancer causing BRCA1 BRCT mutants fail to interact with RAP80 and consequently demonstrate inefficient recruitment to DNA damage sites. Moreover, germline mutations in RAP80 and Abraxas are ...
MKRN2 is a novel ubiquitin E3 ligase for the p65 subunit of NF-κB and negatively regulates inflammatory responses.MKRN2 is a novel ubiquitin E3 ligase for the p65 subunit of NF-κB and negatively regulates inflammatory responses. ...
Any process that activates or increases the frequency, rate or extent of protein ubiquitination involved in ubiquitin-dependent protein catabolic process.
The ubiquitin binding zinc finger (UBZ) domain in the C-terminal portion of Polη has been found to interact with ubiquitin. However, the affinity between the Polη UBZ and ubiquitin was shown to be low with a previously reported Kd of 73-81 μM. This low-affinity binding between Polη UBZ and ubiquitin has been
The ubiquitin ligase (E3) Rsp5p is the only member of the Nedd (neural-precursor-cell-expressed, developmentally down-regulated) 4 family of E3s present in yeast. Rsp5p has several proteasome-independent functions in membrane protein trafficking, including a role in the ubiquitination of most plasma membrane proteins, leading to their endocytosis. Rsp5p is also required for the ubiquitination of endosomal proteins, leading to their sorting to the internal vesicles of MVBs (multivesicular bodies). Rsp5p catalyses the attachment of non-conventional ubiquitin chains, linked through ubiquitin Lys-63, to some endocytic and MVB cargoes. This modification appears to be required for efficient sorting, possibly because these chains have a greater affinity for the ubiquitin-binding domains present within endocytic or MVB sorting complexes. The mechanisms involved in the recognition of plasma membrane and MVB substrates by Rsp5p remain unclear. A subset of Rsp5/Nedd4 substrates have a PY motif and are ...
DNA double-strand breaks (DSBs) not only interrupt the genetic information, but also disrupt the chromatin structure, and both impairments require repair mechanisms to ensure genome integrity. We showed previously that RNF8-mediated chromatin ubiquitylation protects genome integrity by promoting the accumulation of repair factors at DSBs. Here, we provide evidence that, while RNF8 is necessary to trigger the DSB-associated ubiquitylations, it is not sufficient to sustain conjugated ubiquitin in this compartment. We identified RNF168 as a novel chromatin-associated ubiquitin ligase with an ability to bind ubiquitin. We show that RNF168 interacts with ubiquitylated H2A, assembles at DSBs in an RNF8-dependent manner, and, by targeting H2A and H2AX, amplifies local concentration of lysine 63-linked ubiquitin conjugates to the threshold required for retention of 53BP1 and BRCA1. Thus, RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional ...
During ubiquitination, Ub is initially activated by an ATP‐dependent E1 enzyme before it is passed to one of several distinct Ub‐conjugating enzymes (E2s). The E2 subsequently acts to either transfer Ub to a HECT (homologous to the E6AP carboxyl terminus)‐type Ub ligase (E3), or to catalyse substrate ubiquitination in conjunction with RING (really interesting new gene)‐type or U‐box E3 enzymes. An exception to this is the process of coupled monoubiquitination, through which E2 enzymes can catalyse the ubiquitination of Ub‐binding domain (UBD)‐containing proteins independently of E3 (Hoeller et al, 2006, 2007).. Ubiquitin ligases seem to be the crucial determinants of substrate selection and are also considered to be important components in controlling Ub‐chain formation on a substrate. For example, different HECT‐type E3s can specify both the linkage of a Ub chain and the process of its assembly. E6AP can form a Lys 48‐linked chain on its active cysteine residue (Scheffner & ...
We considered two possible explanations for the stu1-5 ubp3Δ synthetic lethality. First, we examined the possibility that Ubp3p plays a role in the cell-cycle regulation of Stu1p. Several mitotic proteins are subject to cell-cycle regulation involving ubiquitin-mediated protein degradation. However, the levels of Stu1p are relatively constant throughout the cell cycle, indicating that it is not a substrate for this specific ubiquitin-dependent pathway.. Next, we considered the possibility that mutant Stu1-5p is an unstable protein that is targeted for ubiquitin-mediated degradation. We showed that the levels of Stu1p in stu1-5 cells are several-fold lower than the levels in wild-type cells. In addition, the temperature sensitivity of stu1-5 can be suppressed by producing wild-type levels of the mutant protein. These results indicate that the temperature sensitivity is caused by reduced levels of Stu1p and not by reduced function. Interestingly, the critical threshold of Stu1-5p protein level ...
Project title: Regulation and control of linear ubiquitin chian synthesis: Structure, function and mechanism of linear ubiquitin chian assembly complex LUBAC. Summary: The linear ubiquitin chain assembly complex LUBAC is E3 ubiquitin ligase that plays pivotal roles in the innitiation of innate and adpative immune response, especially in the activation of nuclear factor-kappa B, which is a transcription factor that induces transcription of inflammatory genes. Abberrant LUBAC activity has been known as a contributor to diffuse large B-cell lymphoma (DLBL), which is a bone marrow malignancy. More importantly, individuals carrying congenital mutaions in LUBAC protein domains (i.e. HOIP, HOIL-1, SHARPIN) manifest devastating immunodeficiency and/or autoinflammatory symptoms. All those add up to the fact that LUBAC is really interesting and important. This project aims to unveal regulatory mechanisms for LUBAC activity with aid from biochemical and structural biology techiniques (i.e. in vitro protein ...
2879 The ubiquitin-proteasome pathway controls the turnover of many oncoproteins and tumor suppressors, thus playing a major role in cancer development. This pathway also regulates the stability of Smads. Recent studies have shown that R-Smads are post-translationally modified by ubiquitin and can be irreversibly removed from the cell by the proteasome-mediated degradation system. Ubiquitination, the covalent attachment of ubiquitin to proteins, predominantly serves to target proteins for their degradation by 26S proteasomes. Conjugation of ubiquitin is accomplished by an enzymatic cascade involving E1, E2 and E3 enzymes. Ubiquitin E3 ligases play the most significant role in substrate specificity. Smad4/DPC4 is a common signal transducer in TGF-β signaling. Contrary to R-Smads, our knowledge on the regulation of Smad4 by ubiquitin/proteasome pathway is rather limited. Although the ubiquitin-proteasome pathway has been established as one mechanism of regulating Smad4 stability, the specific ...
Protein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to proteins being degraded is performed by a reaction cascade consisting of three enzymes, named E1 (ubiquitin activating enzyme), E2 (ubiquitin conjugating enzyme), and E3 (ubiquitin ligase). Each E3 has specificity to its substrate, or proteins to be targeted by ubiquitination. Many E3s are discovered in eukaryotes and they are classified into four types: HECT type, U-box type, single RING-finger type, and multi-subunit RING-finger type. Multi-subunit RING-finger E3s are exemplified by cullin-Rbx E3s and APC/C. They consist of a RING-finger-containing subunit (RBX1 or RBX2) that functions to bind E2s, a scaffold-like cullin molecule, adaptor proteins, and a target recognizing subunit that binds substrates ...
Protein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to proteins being degraded is performed by a reaction cascade consisting of three enzymes, named E1 (ubiquitin activating enzyme), E2 (ubiquitin conjugating enzyme), and E3 (ubiquitin ligase). Each E3 has specificity to its substrate, or proteins to be targeted by ubiquitination. Many E3s are discovered in eukaryotes and they are classified into four types: HECT type, U-box type, single RING-finger type, and multi-subunit RING-finger type. Multi-subunit RING-finger E3s are exemplified by cullin-Rbx E3s and APC/C. They consist of a RING-finger-containing subunit (RBX1 or RBX2) that functions to bind E2s, a scaffold-like cullin molecule, adaptor proteins, and a target recognizing subunit that binds substrates ...
HPK1, a member of mammalian Ste20-like serine/threonine kinases, is lost in |95% pancreatic cancer through proteasome-mediated degradation. However, the mechanism of HPK1 loss has not been defined. The aims of this study are to identify the ubiquitin ligase and to examine the mechanisms that targets HPK1 degradation. We found that the CUL7/Fbxw8 ubiquitin ligase targeted HPK1 for degradation via the 26 S proteasome. The ubiquitination of HPK1 required its kinase activity and autophosphorylation. Wild-type protein phosphatase 4 (PP4), but not the phosphatase-dead PP4 mutant, PP4-RL, inhibits the interaction of Fbxw8 with HPK1 and Fbxw8-mediated ubiquitination of HPK1. In addition, we showed that Thr-355 of HPK1 is a key PP4 dephosphorylation site, through which CUL7/Fbxw8 ubiquitin ligase and PP4 regulates HPK1 stability. Knockdown of Fbxw8 restores endogenous HPK1 protein expression and inhibits cell proliferation of pancreatic cancer cells. Our study demonstrated that targeted degradation of HPK1 by
Ubiquitin was detected within both the cytoplasm and nucleus of the cytotrophoblast layer only. Both monomeric and conjugated forms of ubiquitin were detected. The relative abundance of ubiquitin did not change through gestation or in the two disorders of pregnancy studied. This is the first report to demonstrate the cell-specific localisation of ubiquitin and ubiquitin-protein conjugates in the human cytotrophoblast and provides supportive evidence that ubiquitin may be important during placental development. PMID: 11742419 ...
Irecently returned from the 2013 EMBO Conference on Ubiquitin and Ubiquitin‐like proteins: from structure to function, where I once again marveled at the rapid pace of discovery. From one year to the next, many people have completely new stories to tell and the spirit of the field is one of openness and collegiality. The late Cecile Pickart, a pioneer in ubiquitin research, once referred to ubiquitin as infinitively seductive. I have to agree, in more ways than one. Not only is ubiquitin involved in virtually all aspects of cell biology, but the community goes about its business in a very positive and welcoming manner; an approach not always seen in other areas of the biomedical sciences.. Given the rate at which new knowledge is acquired, and seeing the wealth of primary research published, we were inspired last year to put together a Review Series on Ubiquitylation: mechanism and functions. Some aspects of the latest research were not included-such as the role of ubiquitin in DNA repair, ...
Ubiquitin signaling pathways rely on E3 ligases for effecting the final transfer of ubiquitin from E2 ubiquitin conjugating enzymes to a protein target. Here we re-evaluate the hybrid RING/HECT mechanism used by the E3 family RING-between-RINGs (RBRs) to transfer ubiquitin to substrates. We place RBRs into the context of current knowledge of HECT and RING E3s. Although not as abundant as the other types of E3s (there are only slightly more than a dozen RBR E3s in the human genome), RBRs are conserved in all eukaryotes and play important roles in biology. Re-evaluation of RBR ligases as RING/HECT E3s provokes new questions and challenges the field.
The herpes simplex virus type 1 (HSV-1) encoded E3 ubiquitin ligase, infected cell protein 0 (ICP0), is required for efficient lytic viral replication and regulates the switch between the lytic and latent states of HSV-1. As an E3 ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular targets, allowing the virus to counteract different cellular intrinsic and innate immune responses. In this review, we will focus on how ICP0s E3 ubiquitin ligase activity inactivates the host intrinsic defenses, such as nuclear domain 10 (ND10), SUMO, and the DNA damage response to HSV-1 infection. In addition, we will examine ICP0s capacity to impair the activation of interferon (innate) regulatory mediators that include IFI16 (IFN γ-inducible protein 16), MyD88 (myeloid differentiation factor 88), and Mal (MyD88 adaptor-like protein). We will also consider how ICP0 allows HSV-1 to evade activation of the NF-κB (nuclear factor kappa B) inflammatory signaling pathway. Finally, ICP0s ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Ubiquitination was surprising because tBid-N has no lysine residues that conventionally act as ubiquitin acceptor sites (Fig. S1 B). Typically, ubiquitin can be linked either via a peptide bond to the ε amino group of a lysine residue or to the α amino group of an N-terminal residue (Ciechanover and Ben-Saadon, 2004). Because linkage to lysine was excluded, we investigated whether the N terminus of tBid-N acted as a ubiquitin acceptor site. To this end, tBid-N was fused C-terminally to a tandem affinity purification (TAP) tag, which contains a calmodulin-binding domain and protein A sequence separated by a tobacco etch virus (TEV) protease-sensitive site (ENLYFQG). This allows for two-step purification; first on IgG beads and then after cleavage by TEV on calmodulin beads (Rigaut et al., 1999). In one tBid-N TAP construct (TEV tBid-N TAP 7), sequences encoding the first seven amino acids of tBid-N and a TEV protease site were cloned upstream of the tBid-N coding region (Fig. 3 C). If tBid-N ...
Following a map-based approach, we cloned HVE and found it to encode the Arabidopsis ortholog of mammalian CAND1. The important role of the HVE/CAND1 gene in vascular development has remained unnoticed so far, even though its cloning and the characterization of several mutant alleles have been reported by three research groups (Cheng et al., 2004; Chuang et al., 2004; Feng et al., 2004). Human CAND1 regulates the ubiquitination of target proteins by binding to unneddylated CULLIN1 (CUL1). CUL1, SKP1 and F-box proteins form SCF complexes that ligate ubiquitin moieties to proteins that will be degraded by the 26S proteasome. It has been proposed that the binding of CAND1 to unneddylated CUL1 hinders the interaction of SKP1 with CUL1 preventing the assembly of the SCF complex. After neddylation of CUL1, CAND1 is released and the SFC complex is assembled (Liu et al., 2002; Zheng et al., 2002; Hwang et al., 2003; Oshikawa et al., 2003).. Ubiquitin-mediated protein degradation is essential for auxin ...
TY - JOUR. T1 - Ubiquitin ligases. T2 - Cell-cycle control and cancer. AU - Nakayama, Keiichi I.. AU - Nakayama, Keiko. PY - 2006/5/1. Y1 - 2006/5/1. N2 - A driving force of the cell cycle is the activation of cyclin-dependent kinases (CDKs), the activities of which are controlled by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors. Two ubiquitin ligases, the SKP1-CUL1-F-box-protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C), are responsible for the specific ubiquitylation of many of these regulators. Deregulation of the proteolytic system might result in uncontrolled proliferation, genomic instability and cancer. Cumulative clinical evidence shows alterations in the ubiquitylation of cell-cycle regulators in the aetiology of many human malignancies. A better understanding of the ubiquitylation machinery will provide new insights into the regulatory biology of cell-cycle transitions and the development of anti-cancer drugs.. AB - A ...
Ubiquitin-dependent regulation of endocytosis plays an important part in the control of signal transduction, and a critical issue in the understanding of signal transduction therefore relates to regulation of ubiquitination in the endocytic pathway. We discuss here what is known of the mechanisms by which signaling controls the activity of the ubiquitin ligases that specifically recognize the targets of ubiquitination on the endocytic pathway, and suggest alternative mechanisms that deserve experimental investigation.
... s are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm.[1] The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that carry out such reactions are called proteases. Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. The degradation process yields peptides of about seven to eight amino acids long, which can then be further degraded into amino acids and used in synthesizing new proteins.[2] Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is catalyzed by enzymes called ubiquitin ligases. Once a protein is tagged with a single ubiquitin molecule, this is a signal to other ligases to attach additional ubiquitin molecules. The result is a polyubiquitin chain that ...
MalaCards based summary : Itch E3 Ubiquitin Ligase Deficiency, also known as autoimmune disease, syndromic multisystem, is related to autoimmune disease, multisystem, with facial dysmorphism and autoimmune disease. An important gene associated with Itch E3 Ubiquitin Ligase Deficiency is ITCH (Itchy E3 Ubiquitin Protein Ligase). Affiliated tissues include liver and thyroid ...
Ubiquitin-binding protein that interacts with the BRCA1-BARD1 heterodimer, and regulates its activity. Specifically binds Lys-6-linked polyubiquitin chains. Interaction with autoubiquitinated BRCA1, leads to inhibit the E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer. Component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol ...
ubiquitin protein ligase activity, proteasome-mediated ubiquitin-dependent protein catabolic process, protein polyubiquitination, protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Ubiquitin과 Protein의 접합은 Stability와 Activity, Localization 등의 환경에 의해 변화할 수 있습니다.. 거의 모든 Protein은 Life cycle의 어느 시점에 Ubiquitylated 되지만, 3 종류의 Enzyme이 관여하게 됩니다.. E1 Activating enzyme은 Ubiquitin을 E2 Conjugation enzyme에 전달하거나 활성화시킵니다.. 이후 E2 Enzyme은 E3 Ligase 도움하에 직, 간접적으로 Ubiquitin을 기질로 보내며 E3는 기질 단백질에 결합하여 강한 선택성을 가지고 Ubiquitination으로 표지할 기질단백질을 인지합니다.. Deregulated E3 ligase는 암, 바이러스 감염, 관절염 등 다양한 부분에 심각한 질병을 일으킵니다.. 따라서 이러한 연구는 혁신적인 치료제 개발에 많은 도움을 줄 것입니다. ...
Ubiquitination is a post-translational modification in which one or more 76 amino acid polypeptide ubiquitin molecules are covalently linked to the lysine residues of target proteins. Ubiquitination is the main pathway for protein degradation that governs a variety of eukaryotic cellular processes, including the cell cycle, vesicle trafficking, antigen presentation and signal transduction. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of many diseases including inflammatory and neurodegenerative disorders. Recent studies have revealed that viruses and bacterial pathogens exploit the host ubiquitination pathways to gain entry and to aid their survival/replication inside host cells. This review will summarize recent developments in understanding the biochemical and structural mechanisms utilized by bacterial pathogens to interact with the host ubiquitination pathways.
Ubiquitin binding of OspG is required for inhibiting host NF-κB signaling during Shigella infection.(A) The role of OspG in recruitment of ubiquitin to intrace
Endosomal protein that forms a complex with Hse1p; required for recycling Golgi proteins, forming lumenal membranes and sorting ubiquitinated proteins destined for degradation; has Ubiquitin Interaction Motifs which bind ubiquitin (Ubi4p ...
Chemical Synthesis of Ubiquitinated Peptides with Varying Lengths and Types of Ubiquitin Chains to Explore the Activity of Deubiquitinases | Dr. Sudhir N. Bavikar; Liat Spasser; Mahmood Haj-Yahya; Dr. Subramanian Vedhanarayanan Karthikeyan; Tal Moyal; Dr. K. S. Ajish Kumar; Prof. Ashraf Brik | download | BookSC. Download books for free. Find books
The meeting will discuss the functional roles of the ubiquitin system, how it works to ensure normal signal transduction, what are the pathological consequences when it is perturbed and how we may be able to address such perturbance therapeutically in various diseases including cancer, autoimmunity and neurodegeneration.. Confirmed speakers include Michael Rape (UC Berkeley), Ivan Dikic (Frankfurt Center for Autophagy and Ubiquitin Research - FCAR), Kim Newton (Genentech Inc), Domagoj Vucic (Genentech Inc), Eric Bennett (UC San Diego), Florian Bassermann (Technical University of Munich), Mads Gyrd-Hansen (Ludwig Institute for Cancer Research), Helle Ulrich (Institute of Molecular Biology - IMB), Eric Baehrecke (UMass Medical School), Pascal Meier (ICR London), Anne Bertolotti (LMB Cambridge), Richard Youle (NIH), Jonathon Pines (ICR London) and Geert van Loo (VIB-UGent Center for Inflammation Research).. Conference website: https://www.fusion-conferences.com/conference77.php. ...
Click to launch & play an online audio visual presentation by Prof. Allen Taylor on Ubiquitin dependent degradation of proteins modified by oxidation, deamidation and glycation: role in vision, part of a collection of online lectures.
Predicted to have thiol-dependent ubiquitinyl hydrolase activity and zinc ion binding activity. Predicted to be involved in protein deubiquitination and ubiquitin-dependent protein catabolic process. ... Predicted to have thiol-dependent ubiquitinyl hydrolase activity and zinc ion binding activity. Predicted to be involved in protein deubiquitination and ubiquitin-dependent protein catabolic process. Predicted to localize to the cytoplasm. Orthologous to human USP3 (ubiquitin specific peptidase 3). ...
In my laboratory, we use mammalian cells and protozoan parasite as model systems to address questions in the area of Molecular Cell biology in Health and Disease. We have special interest in inter-disciplinary studies at the interface between molecular and cell biology to understand the role of ubiquitin system in the control of cellular functions. The current interests include. (a) regulation of cell cycle and the role of ubiquitin proteasome pathway,. (b) protein quality control mechanisms,. (c) host-pathogen interaction and. (d) unraveling the ubiquitin pathway mediated cellular processes that control the transformation of one development stage to another in protozoan parasites. ...
Shp1 and Ubx2 are adaptors of Cdc48 involved in ubiquitin-dependent protein degradation.: Known activities of the ubiquitin-selective AAA ATPase Cdc48 (p97) req
The yeast ubiquitin-like and ubiquitin-associated protein Dsk2 is one of the ubiquitin receptors that function in the ubiquitin-proteasome pathway. We screened the Dsk2-interacting proteins in Saccharomyces cerevisiae by a two-hybrid assay and identified a novel Dsk2-interacting protein, Irc22, the gene locus of which has previously been described as YEL001C, but the function of which is unknown. IRC22/YEL001C encodes 225 amino acid residues with a calculated molecular weight of 25 kDa. The Irc22 protein was detected in yeast cells. IRC22 was a nonessential gene for yeast growth, and its homologs were found among ascomycetous yeasts. Irc22 interacted with Dsk2 in yeast cells, but not with Rad23 and Ddi1. Ubiquitin-dependent degradation was impaired mildly by over-expression or disruption of IRC22. Compared with the wild-type strain, dsk2D exhibited salt sensitivity while irc22D exhibited salt tolerance at high temperatures. The salt-tolerant phenotype that was observed in irc22D disappeared in the
FIGURE 1. E3 ubiquitin ligases and DUBs involved in CD4+ T cell identity. After T cell activation by an activated APC, a naive T cell can differentiate into any of the CD4+ effector cell fates shown. All of the key transcriptional factors that regulate these effector fates can be regulated directly or indirectly via ubiquitylation. ...
The transforming growth factor β (TGFβ) superfamily of signal transduction molecules plays crucial roles in the regulation of cell behavior. TGFβ regulates gene transcription through Smad proteins and signals via non-Smad pathways. The TGFβ pathway is strictly regulated, and perturbations lead to tumorigenesis. Several pathway components are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. Smurfs are well known negative regulators of TGFβ, which function as E3 ligases recruited by adaptors such as I-Smads. TGFβ signaling can also be enhanced by E3 ligases, such as Arkadia, that target repressors for degradation. It is becoming clear that E3 ligases often target multiple pathways, thereby acting as mediators of signaling cross-talk. Regulation via ubiquitination involves a complex network of E3 ligases, adaptor proteins, and deubiquitinating enzymes (DUBs), the last-mentioned acting by removing ubiquitin from its targets. Interestingly, also non-degradative ...
Ubiquitin, clone: eBioP4D1 (P4D1), eBioscience™ 100μg; Unconjugated Ubiquitin, clone: eBioP4D1 (P4D1), eBioscience™ Primary Antibodies U
Here, we uncover a new class of substrates of the ERAD ubiquitin ligase Doa10. These are proteins that contain a hydrophobic hairpin and that localize to ER and LD membranes. By degrading specifically the ER pool, ERAD restricts their localization to LDs, thereby contributing to maintain the individual membrane identities of the ER and LDs. These findings reveal a function for the ERAD pathway that is distinct from its role in protein quality control or in lipid‐dependent degradation of sterol enzymes (Ruggiano et al, 2014). We call this novel function "protein spatial control" since it leads to the degradation of a protein based on its localization rather than its folding status.. The involvement of quality control systems in the degradation of mislocalized proteins has been described in different contexts. For example, tail‐ and GPI‐anchored proteins failing to insert in the ER membrane are selectively targeted for degradation (Hessa et al, 2011; Ast et al, 2014; Rodrigo‐Brenni et al, ...
Caltag Medsystems provide ubiquitin reagents and antibodies for the study of the ubiquitin-proteasome system, including recombinant proteins and peptides, Proteosome/deubiquitinase inhibitors, Ubiquitination kits, and ubiquitination inhibitors.