ABSTRACT: INTRODUCTION: The seven in absentia homolog 2 (SIAH2) protein plays a significant role in the hypoxic response by regulating the abundance of hypoxia-inducible factor-alpha; however, its role in breast carcinoma is unclear. We investigated the frequency and expression pattern of SIAH2 in two independent cohorts of sporadic breast cancers. METHODS: Immunohistochemical evaluation of SIAH2protein expression was conducted in normal breast tissues and in tissue microarrays comprising ductal carcinoma in situ (DCIS) and a cohort of invasive breast carcinomas. Correlation analysis was performed between SIAH2 and clinicopathological variables and intrinsic breast cancer subgroups and validated in a cohort of 293 invasive ductal carcinomas. Promoter methylation, gene copy number and mRNA expression of SIAH2 were determined in a panel of basal-like tumors and cell lines. RESULTS: There was a significant increase in nuclear SIAH2 expression from normal breast tissues through to DCIS and progression to
The N-end rule pathway is a proteolytic system where its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an important part of specific degrons called N-degrons. like a scaffold E3 that promotes HR6B/UbcH2-reliant ubiquitylation of H2A and H2B however not H3 and H4 via a system distinct from normal polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is activated by dipeptides bearing destabilizing N-terminal residues allosterically. Insufficient monoubiquitylation and polyubiquitylation on UBR2-lacking meiotic chromosomes correlate to problems in dual strand break (DSB) restoration along with other meiotic procedures leading to pachytene arrest at stage IV and apoptosis. A few of these features of UBR2 are found in somatic cells where UBR2 is really a chromatin-binding proteins involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities ...
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Specifically ubiquitinates Lys-63 in target proteins (By similarity). Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Involved in ubiquitination of ERBB4 intracellular domain E4ICD1 (PubMed:19193720). Predominantly involved in ubiquitination of membrane bound forms of ERBB4 rather than processed precursors and intermediate membrane-anchored 80 kDa fragments (m80HER4), with a lesser role in ubiquitination of ERBB4 intracellular domain E4ICD1 (PubMed:19047365). Promotes ubiquitination of RAPGEF2. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Part of a signaling complex composed of NEDD4, RAP2A and TNIK
The SIAH1 gene encodes a RING-type E3 ubiquitin ligase belonging to the Seven in Absentia Homolog (SIAH) family. The enzyme carries out the ubiquitination of a wide variety of targets, either by direct binding or by acting as the essential RING domain subunit for larger E3 ubiquitin ligase complexes. By carrying out its function, the protein marks its targets for proteasomal degradation. Target substrates of SIAH1 include transcription regulators such as ELL2, MYB, POU2AF1, PML and RBBP8, the signal transduction molecules TIEG1 and NUMB, the cell surface receptor DCC and the anti-aopoptotic protein BAG1. It also ubiquitinates SYP, a protein involved in synaptic vesicle function in neurons. The protein is thus involved in the regulation of several key biological processes such as apoptosis, axon guidance, cell cycle, spermatogenesis and nervous system development. ...
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
Parkin is encoded by the PARK2 gene in humans; its precise function is unknown. However, it is known to be part of a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. The ubiquitin-tagged proteins are then degraded by ubiquitin-proteasome complexes. Mutations in the PARK2 gene are associated with familial and autosomal recessive juvenile forms of Parkinson disease. It has been suggested that loss of function of the parkin protein leads to dopaminergic cell death, but the mechanism is not clear. Parkin is also known as Parkinson protein 2, E3 ubiquitin protein ligase; Parkinson disease (autosomal recessive, juvenile) 2, parkin; E3 ubiquitin-protein ligase parkin, Parkinson disease protein 2, PDJ, PRKN, AR-JP, and LPRS2.. ...
Parkin is encoded by the PARK2 gene in humans; its precise function is unknown. However, it is known to be part of a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. The ubiquitin-tagged proteins are then degraded by ubiquitin-proteasome complexes. Mutations in the PARK2 gene are associated with familial and autosomal recessive juvenile forms of Parkinson disease. It has been suggested that loss of function of the parkin protein leads to dopaminergic cell death, but the mechanism is not clear. Parkin is also known as Parkinson protein 2, E3 ubiquitin protein ligase; Parkinson disease (autosomal recessive, juvenile) 2, parkin; E3 ubiquitin-protein ligase parkin, Parkinson disease protein 2, PDJ, PRKN, AR-JP, and LPRS2.. ...
Attempts to target mutant KRAS have been unsuccessful. Most of the current therapeutic approaches are indirect, mainly via inhibiting KRAS down-stream signaling, which have been marginally successful. Here we report the identification of Smad ubiquitination regulatory factor 2 (SMURF2), a HECT-type ubiquitin ligase (E3) as a critical regulator of mutant KRAS protein stability. We show that the loss of SMURF2 either by si-/sh-RNA mediated gene silencing or by overexpression of a catalytically inactive SMURF2 Cys716Ala (CA) mutant, can cause lysosome-mediated KRAS degradation; whereas, overexpression of wild type SMURF2 enhances KRAS protein stability. Most importantly, we found that mutant KRAS protein is more susceptible to SMURF2 alterations in that mutant protein half-life decreased from ,12h in control siRNA-treated cells to ,3h with Smurf2 siRNA treatment, whereas only marginal differences were noted for wild-type KRAS protein upon similar treatments. Importantly, this loss of mutant KRAS ...
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E3 ubiquitin ligases have a significant role in carcinogenesis and include a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome. ubiquitin ligases for GC are discussed IPI-493 in the review. (a very interesting new gene) fingers IPI-493 and U-box domains[21]. There are about 30 proteins containing the HECT domain. The fingers and U-box quitin ligases contain the new gene (finger domain but only a small part functions as an E3 ubiquitin ligase. Unlike RING proteins most HECT proteins if not all are believed to function as E3 ubiquitin ligases. RING and HECT E3 ubiquitin ligases use different catalytic mechanisms to promote the transfer of ubiquitin to targeted substrates. RING E3 ubiquitin ligases can promote the direct transfer of ubiquitin from E2 to the targeted substrate whereas HECT E3 ubiquitin ligases interact with the cognate E2 followed by the formation of a thiolester linkage with ubiquitin and subsequent ...
The PARK2 gene encodes the Parkin protein. It is one of three genes that protect from young-onset Parkinson disease (PD); in Parkins absence, symptoms and signs usually begin before the age of forty. Despite the genes discovery in 1998 by Kitada et al., few Parkin-specific antibodies exist. The antibodies available do not readily detect specific, modified forms of Parkin and higher-order variants that are found in the human brain. The lack of variant-specific tools has limited progress and understanding of Parkins functions in the human brain in both healthy and diseased states.. Hypothesis: ...
E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. It probably triggers the ubiquitin-mediated degradation of different substrates.
The parkin gene, PARK2, contains 12 exons and 1.5 Mb [2]. PARK2 is located on a region of chromosome 6 that is known to be fragile and unstable; making it prone to mutations and deletions [1]. Genetically acquiring a mutation in PARK2 can lead to developing early onset autosomal recessive Parkinsons Disease (PD). The protein is an E3 ubiquitin ligase, which functions as a component of the ubiquitin proteasome degradation system. It consists of 465 amino acids, an ubiquitin-like domain, and two RING finger domains [1]. Ubiquitination (and polyubiquitination) marks proteins to be degraded by the proteasome. Mutations of parkin can result in the loss of this function and endanger the cell. Studies have shown that improper protein degradation can cause a build-up of parkin substrates and neuronal death of the cells producing dopamine. Mitochondrion function and integrity is also upheld by the parkin protein, but the link between parkin, mitochondria, and PD is still being investigated [4]. Overall, ...
Read "Overexpression of OsRDCP1 , a rice RING domain-containing E3 ubiquitin ligase, increased tolerance to drought stress in rice ( Oryza sativa L.), Plant Science" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
... , Authors: Jianfei Qi, Zeev Ronai. Published in: Atlas Genet Cytogenet Oncol Haematol.
Here, we show that cardiomyocyte Parkin is essential to mitochondrial and cardiac hemostasis in Drosophila. This warrants re-evaluation of the notion, derived from absence of a basal cardiac phenotype in parkin null mice,16 that Parkin is dispensable to normal heart function. By interrogating genetic epistasis between Drosophila Parkin and mitofusin (MARF), we uncover a completely new mechanism for end-organ dysfunction produced by Parkin insufficiency: ongoing mitochondrial fusion contributes to mitochondrial contagion when Parkin signaling (and presumably Parkin-dependent mitophagic elimination of abnormal organelles) is impaired. These findings suggest that general mitochondrial health and end-organ function could be preserved in mitophagically impaired tissues through chronic suppression of fusion-induced mitochondrial contamination.. The PINK1-Parkin interaction is central to mitophagic quality control in most tissues, but published studies provide an inconsistent picture of the role of ...
The most common mode of healthcare delivery is through personal, face-to-face contact between a healthcare provider and a beneficiary (patient). There is, however, an increasing trend towards the provision of healthcare in the absence of personal contact. This limit of contact during patient care is known as in absentia health care. In Absentia healthcare, or distance medicine, occurs when the patient and care giver are at different locations, but still communicate by audio and video, or sometimes without any personal contact. A face-to-face contact is often a necessary prelude to rendering health care. This, however, may not be necessary for care; in fact current technologies permit with no prior or concurrent contact.[1][2] Some people argue that this type of in absentia medical care may derail the traditional sequences of examination, diagnosis and treatment, and that such a detour may challenge existing values of modern medicine. In absentia care assumes heightened relevance today because ...
Mutations in the parkin gene, which encodes a ubiquitin ligase, has been implicated as one of causative factor for genetic parkinsonism. Interestingly, parkin role has also been implicated in cancer as a putative tumor suppressor with the gene been frequently targeted by deletion and inactivation in several human malignant tumors. Here, we demonstrated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells and that the restoration of parkin expression promoted G1 phase cell-cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Furthermore, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin-null mouse model exhibited increased levels of cyclin D1, VEGF receptor, and Akt phosphorylation, and divided significantly ...
E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation ...
The E3 Ubiquitin-protein Ligases Are Associated To Various Processes Such As Cell Cycle Control And Diverse Developmental Pathways. Arabidopsis Thaliana SEVEN IN ABSENTIA Like 7, Which Has Ubiquitin Ligase Activity, Is Located In The Nucleus And Cytosol
Heart failure is a major complication of cardiovascular disease that frequently involves initial cardiac hypertrophy that provides transient compensation for decreased heart function. Eventually, decompensation leads to compromised cardiac structure and progression into heart failure. Investigation of the downstream effector pathways for these growth factors has identified molecules involved in the progression of cardiac hypertrophy and heart failure, including phosphoinositide 3-kinase (PI3K) and Akt (Protein Kinase B). MG53, a tripartite motif (TRIM) protein family member designated as TRIM72, is highly expressed in skeletal and cardiac muscle and is known to have cardioprotective effects through modulation of PI3K signaling mechanisms. It is essential for the activation of PI3K-mediated intracellular signaling in cardiomyocytes and TRIM72 overexpression is sufficient to induce PI3K signaling. As TRIM72 regulates PI3K signaling it may play a role in regulation of heart failure, which is ...
The TRIM37 (also known as MUL) gene is located in the 17q23 chromosomal region, which is amplified in up to approximately 40% of breast cancers. TRIM37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases, but its protein substrate(s) is unknown. Here we report that TRIM37 mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression. We find that in human breast cancer cell lines containing amplified 17q23, TRIM37 is upregulated and, reciprocally, the major H2A ubiquitin ligase RNF2 (also known as RING1B) is downregulated. Genome-wide chromatin immunoprecipitation (ChIP)-chip experiments in 17q23-amplified breast cancer cells identified many genes, including multiple tumour suppressors, whose promoters were bound by TRIM37 and enriched for ubiquitinated H2A. However, unlike RNF2, which is a subunit of polycomb repressive complex 1 (PRC1), we find that TRIM37 associates with polycomb repressive complex 2 (PRC2). TRIM37, PRC2 and PRC1 are co-bound to
Exit from mitosis requires the degradation of regulatory proteins including the mitotic cyclins and securin through ubiquitination by the anaphase promoting complex bound to Cdc20 or Cdh1. Cdc20-APC is regulated through inhibition by the spindle assembly checkpoint protein MAD2. Knowledge of Cdh1-APC regulation is limited to the phosphorylation-dependent dissociation of Cdh1 from APC. A novel means of regulating Cdh1 by the MAD2-related gene, MAD2L2, is reported. MAD2L2 specifically binds and inhibits Cdh1-APC, paralleling the effect of MAD2 on Cdc20. It is suggested that MAD2L2 and MAD2 inhibit the release of substrates from APC and a mechanism of inhibition is proposed (Pfleger, 2001a). The specificity of ubiquitin-mediated protein degradation with regard to the selection of substrates to be polyubiquitinated has only been determined rather recently. Substrate targeting by the N-end rule and HECT (homology to E6AP carboxyl terminus) domain ubiquitin ligases occurs through substrate-specific ...
Ndfip1 is an adaptor for the E3 ubiquitin ligase Itch. Both Ndfip1- and Itch-deficient T cells are biased toward Th2 cytokine production. In this study, we demonstrate that lungs from Ndfip1−/− mice showed increased numbers of neutrophils and Th17 cells. This was not because Ndfip1−/− T cells are biased toward Th17 differentiation. In fact, fewer Ndfip1−/− T cells differentiated into Th17 cells in vitro due to high IL-4 production. Rather, Th17 differentiation was increased in Ndfip1−/− mice due to increased numbers of IL-6-producing eosinophils. IL-6 levels in mice that lacked both Ndfip1 and IL-4 were similar to wild-type controls, and these mice had fewer Th17 cells in their lungs. These results indicate that Th2 inflammation, such as that observed in Ndfip1−/− mice, can increase Th17 differentiation by recruiting IL-6-producing eosinophils into secondary lymphoid organs and tissues. This may explain why Th17 cells develop within an ongoing Th2 inflammatory response. ...
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Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also ...
WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 4 tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. The encoded protein belongs to a family of NEDD4-like proteins, which are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Alternative splicing of this gene generates at least 6 transcript variants; however, the full length nature of these transcripts has not been defined. [provided by RefSeq, Jul 2008 ...
Translation is important in the regulation of gene expression and is implicated in the control of cell growth, proliferation, and differentiation (32-34). In eukaryotes, initiation is the rate-limiting step of translation under most circumstances, and initiation is a major target for regulation (33). Paip1 is a mammalian PABP that binds to eIF4A and eIF3 and stimulates translational initiation. In the present study, we showed that the Paip1 protein was degraded by the HECT ubiquitin ligase WWP2. The following findings from the present study directly support the use of Paip1 as a physiological substrate of WWP2. WWP2 directly interacted with Paip1, and the interaction depended on the integrity of the WW domain of WWP2. The loss of WWP2 impeded Paip1 turnover. WWP2 promoted Paip1 ubiquitination both in vivo and in a reconstituted in vitro system. The ubiquitin ligase activity of WWP2 and the PXXY motif of Paip1 were critical for ubiquitination and degradation. Previous studies have demonstrated ...
E3 Ubiquitin-Protein Ligase XIAP (Baculoviral IAP Repeat-Containing Protein 4 or IAP-Like Protein or X-Linked Inhibitor Of Apoptosis Protein or XIAP or EC
RBR E3 ubiquitin Ub transfer mechanism Insights into the steps of the RBR mechanism that involve the E2~Ub have been forthcoming from recent studies and structures [47], [48], [50], [54]. Several RBR E3s have been shown to be active with more than one E2 [6], [23], [32], [34], [35], [36], [37], [54], [59], [60], [61], but a full description of the cadre of E2s (there are more than 30 in humans) that work with each human RBR E3 is not yet available. Two available structures of RBR E3s in complex with E2~Ub include the two well-characterized human E2s, Ube2D2 (UbcH5b) and Ube2L3 (UbcH7). Importantly, UbcH5 (and most other E2s) can perform both transthiolation reactions and aminolysis reactions, explaining how it can be active with either RBR E3s or RING-type E3s [34], [35], [36], [59], [60], [61]. The human E2 UbcH7 is a more specialized enzyme that solely performs transthiolation reactions [34], implying that it can function with HECT- and RBR-type E3s, but not with RING-type E3s. Paradoxically, ...
To study the in vivo behavior of restored Parkin expression in H460 cells, we injected 1 × 106 cells infected with either EGFP or Parkin lentiviruses s.c. into the flanks of 6-week-old female nude mice. Tumor cells transduced with virus particles containing Parkin or EGFP alone showed no significant differences in their ability to proliferate over the course of 96 h (Fig. 3)⇓ . High levels of ectopic gene expression were maintained in nearly 100% of the cells examined by flow cytometry and Western analysis before injection (data not shown). After injection, mice were monitored for up to 5 weeks, and tumor volumes were measured with a metric caliper (Fig. 3)⇓ . As shown, the tumor volume of H460 cells infected with the Parkin virus was reduced ∼3-4-fold relative to the controls. Thus, Parkin alone has significant tumor-suppressor activity in H460 cells deficient in the Parkin protein (11) .. Homozygous deletions of exon 2 of Parkin, a gene implicated in autosomal recessive juvenile ...
The RING Domain Proteins BRCA1 And BARD1 Comprise A Heterodimeric Ubiquitin (E3) Ligase That Is Required For The Accumulation Of Ubiquitin Conjugates At Sites Of DNA Damage And For Silencing At DNA Satellite Repeat Regions. Despite Its Links To Chromatin,
Bonilla-Ramirez L, Jimenez-Del-Rio M, Velez-Pardo C. Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: Implication in autosomal recessive juvenile Parkinsonism. Gene. 2012 Oct 6. pii: S0378-1119(12)01229-2. doi: 10.1016/j.gene.2012.09.120. PubMed PMID: 23046578 ...
Opens the Highlight Feature Bar and highlights feature annotations from the FEATURES table of the record. The Highlight Feature Bar can be used to navigate to and highlight other features and provides links to display the highlighted region separately. Links in the FEATURES table will also highlight the corresponding region of the sequence. More... ...
Neurotransmission in the brain critically depends on the maintenance of synapses as well as on regulated synaptic protein turnover. How synaptic proteostasis is held in check has remained largely enigmatic. A new paper in The EMBO Journal reports that the active zone proteins Piccolo and Bassoon put a brake on presynaptic protein turnover by restraining the activity of the E3 ubiquitin ligase Siah1, thereby preventing neurodegeneration.. To retain memories, neurons have evolved mechanisms of activity‐dependent plasticity that involve remodelling of the synaptic proteome in response to internal or external cues. For example, the rapid re‐organization of proteins at synaptic release sites, termed as active zones (AZ), may be utilized for the activity‐dependent modulation of neurotransmission. Several mechanisms have been proposed for synaptic protein turnover, including local protein synthesis and degradation. Considerable attention has been paid to protein synthesis (Martin et al, 1997; ...
Parkin and DJ-1 are two multi-functional proteins linked to autosomal recessive early-onset Parkinsons disease (PD) that were shown to functionally interact by yet unknown mechanisms. We have delineated the mechanisms by which parkin controls DJ-1. Thus, parkin modulates DJ-1 transcription and protein levels via a signaling cascade involving p53 and the endoplasmic reticulum (ER)-stress-induced active X-box-binding protein-1S (XBP-1S). Parkin triggers the transcriptional repression of p53 while p53 down-regulates DJ1 protein and mRNA expressions. We show that parkin-mediated control of DJ-1 is fully p53 dependent. Furthermore, we establish that p53 lowers the protein and mRNA levels of XB-1S. Accordingly, we show that parkin ultimately up-regulates XBP-1 levels. Subsequently, XBP-1 physically interacts with DJ-1 promoter, thereby enhancing its promoter trans-activation, mRNA levels and protein expression. This data was corroborated by the examination of DJ-1 in both parkin and p53 null mice ...
The E3 ubiquitin ligase RNF43 (RING finger protein 43) is an important negative modulator of the WNT signalling pathway that acts at the plasma membrane by targeting Frizzled and its co-receptor LRP for degradation. In the ...
Misfolded proteins compromise cellular function and cause disease. How these proteins are detected and degraded is not well understood. Here we show that PML/TRIM19 and the SUMO-dependent ubiquitin ligase RNF4 act together to promote the degradation of misfolded proteins in the mammalian cell nucleu …
Gene Information This gene encodes a member of the WD-protein subfamily. The encoded protein contains five WD-repeats spanning most of the protein and an SOCS box in the C-terminus. The SOCS box may act as a bridge between specific substrate-binding domains and E3 ubiquitin protein ligases. [provided by RefSeq Jul 2008]. ...
RIG-I and MDA5 are cytoplasmic sensors that recognize different species of viral RNAs, leads to activation of the transcription factors IRF3 and NF-κB, which collaborate to induce type I interferons. In this study, we identified REUL, a RING-finger protein, as a specific RIG-I-interacting protein. REUL was associated with RIG-I, but not MDA5, through its PRY and SPRY domains. Overexpression of REUL potently potentiated RIG-I-, but not MDA5-mediated downstream signalling and antiviral activity. In contrast, the RING domain deletion mutant of REUL suppressed Sendai virus (SV)-induced, but not cytoplasmic polyI:C-induced activation of IFN-β promoter. Knockdown of endogenous REUL by RNAi inhibited SV-triggered IFN-β expression, and also increased VSV replication. Full-length RIG-I, but not the CARD domain deletion mutant of RIG-I, underwent ubiquitination induced by REUL. The Lys 154, 164, and 172 residues of the RIG-I CARD domain were critical for efficient REUL-mediated ubiquitination, as well as the
Mahogunin is an important mediator of chromogenesis and neurodegeneration. Mahoganoid is a mutation of the mahogunin gene, which causes a pleiotropic phenotype that includes suppression of obesity, spongiform neurodegeneration and improvement of insu
Ubiquitin Ligase RNF20/40 Facilitates Spindle Assembly and Promotes Breast Carcinogenesis through Stabilizing Motor Protein Eg5 Researchers have uncovered an important spindle assembly role of the RNF20/40 complex, and implicated the RNF20/40-Eg5 axis in breast carcinogenesis, supporting the pursuit of these proteins as potential targets for breast cancer therapeutic interventions. [Nat Commun] Full Article Stratification and Therapeutic Potential of PML in Metastatic Breast Cancer Researchers showed that promyelocytic leukemia protein (PML) is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumors is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. [Nat Commun] Full Article Interleukin-30 Promotes Breast Cancer Growth and Progression The inflammatory tissue microenvironment which promotes the development of breast cancer (BRCA) is not fully understood. Researchers reported a role for elevated ...
Albert, T.K.; Hanzawa, H.; Legtenberg, Y. I.A.; de Ruwe, M.J.; van den Heuvel, F.A.J.; Collart, M.A.; Boelens, R.; Timmers, H.T.M ...
Complete information for UBR1 gene (Protein Coding), Ubiquitin Protein Ligase E3 Component N-Recognin 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
The RASSF1A tumor suppressor is one of the most commonly inactivated genes in cancer. To understand why epigenetic silencing of RASSF1A promotes tumorigenesis, I employed a loss of function approach to elucidate the role ...
Rabbit anti parkin (pSer378) antibody recognizes E3 ubiquitin-protein ligase parkin (parkin), also known as Parkinson juvenile disease pro
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Smurf2 - Smurf2 (untagged ORF) - Rat SMAD specific E3 ubiquitin protein ligase 2 (Smurf2), (10 ug) available for purchase from OriGene - Your Gene Company.
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Complete information for SIAH2 gene (Protein Coding), Siah E3 Ubiquitin Protein Ligase 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium