Ubiquitin-dependent degradation of hormone receptors is emerging as a key mechanism that regulates the magnitude and duration of hormonal effects on cells and tissues. The pituitary hormone prolactin (PRL) is involved in regulating cell differentiation, proliferation, and survival. PRL engages its receptor (PRLR) to initiate various signaling cascades, including the phosphorylation and activation of Stat5. We found that PRL promotes interaction between PRLR and the F-box protein beta-TrCP2, which functions as a substrate recognition subunit of the SCF(beta-TrCP) E3 ubiquitin ligase. This interaction requires PRLR phosphorylation and the integrity of serine 349 within a conserved motif, which is similar to conserved motifs present in other substrates of SCF(beta-TrCP). The PRLR(S349A) mutant is resistant to ubiquitination and is more stable than its wild-type counterpart. Phosphorylated PRLR undergoes ubiquitination by SCF(beta-TrCP) in vitro. Knockdown of beta-TrCP expression inhibits the ubiquitination

NMR studies of the phosphorylation motif of the HIV-1 protein Vpu bound to the F-box protein beta-TrCP. Related Articles NMR studies of the

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Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Probably recognizes and binds to phosphorylated target proteins (By similarity). In the wing and eye, negatively regulates cell growth and proliferation by mediating the degradation of Myc and cyclin E, respectively (PubMed:11565033, PubMed:15182669). Required for endocycles, but not mitosis in follicle cell epithelium (PubMed:15175253).

NF-kappaB transcription factor is activated upon ubiquitination and subsequent proteolysis of its inhibitor IkappaB. The phosphorylation-dependent ubiquitination is mediated by SCF E3 ubiquitin ligase. In this study, we identified a novel murine F-box/WD40 repeat-containing protein, mHOS (a homologue of HOS/betaTrCP2). mHOS efficiently binds Skp1 protein (a core component of SCF ubiquitin ligase), and phosphorylated IkappaB(alpha). We found that mHOS associates with SCF-ROC1 E3 ubiquitin ligase activity. We have also observed that mHOS is overexpressed in chemically-induced mouse skin tumors, and its overexpression (but not accelerated IkappaB phosphorylation) coincides with the accelerated degradation of IkappaB in vivo. The role of mHOS in the constitutive activation of NF-kappaB in skin carcinogenesis is discussed. ...

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This gene encodes a glutamate-rich protein that contains five WD-repeat motifs. The encoded protein may play a critical role in ribosome biogenesis and may also play a role in histone methylation through interactions with CUL4-DDB1 ubiquitin E3 ligase. [provided by RefSeq, Feb 2012 ...

To examine the proposition that FLJ12973 is involved in colorectal cancer we analysed 31 tumours for sequence variation. No missense changes or pathogenic mutations--truncating or splice site--were detected in any of the tumours ...

p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...

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WD40 domain is one of the most abundant domains and is one of the most active domains of the eukaryotes. Their functions are deeply involved in cellular processes by playing a crucial role as hubs in cellular networks. WD40 Domain regulates diverse protein-protein interactions, especially those that scaffold. They are present in processes such as signal transduction, cell division, chemotaxis, RNA processing, and cytoskeleton construction. WD40 domains were first discovered in bovine beta-transducin, a subunit of the trimeric G protein transducin complex. It contains a series of sequence of approximately 44-60 residues with folds into seven-bladed beta-propellers. Each blade is designed in a four-stranded anti-parallel beta-sheet. WD40 is naturally exploited as seemingly more suitable than other domain candidates because it structurally more compelling. This means that WD40 domains form structures that are highly symmetrical in comparison to other domains that are involved in intracellular ...

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These β-TrCP2|sup|f|/sup| β-TrCP1|sup|-|/sup| mice harbor two mutations; the β-TrCP2 floxed allele (|i|Fbxw11|sup|tm1.1Ybn|/sup||/i|) and the β-TrCP1 knockout allele (|i|Btrc|sup|tm1Paga|/sup||/i|). These mice are a Cre recombinase-inducible double knockout of β-TrCP function and allow study of multiple cellular processes (Wnt pathway, NF-κB pathway, cell cycle regulation, DNA damage response) and cancer.

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InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.

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Slevin, M and Matou, S and Zeinolabediny, Y and Corpas, R and Weston, R and Liu, D and Boras, E and Di Napoli, M and Petcu, E and Sarroca, S and Popa-Wagner, A and Love, S and Font, MA and Potempa, LA and Al-baradie, R and Sanfeliu, C and Revilla, S and Badimon, L and Krupinski, J ...

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Slevin, M and Matou, S and Zeinolabediny, Y and Corpas, R and Weston, R and Liu, D and Boras, E and Di Napoli, M and Petcu, E and Sarroca, S and Popa-Wagner, A and Love, S and Font, MA and Potempa, LA and Al-baradie, R and Sanfeliu, C and Revilla, S and Badimon, L and Krupinski, J ...

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SC9302X Z48179 37552bp DNA PLN 07-FEB-1995 S.cerevisiae chromosome IV cosmid 9302. ABC transporter; ARO1; beta-transducin; fimbrim; HPR1; multidrug resistance; pentafunctional arom polypeptide; reduced growth phenotype; RGP1; SCA6; ubiquitin. SCCHRIII X59720 S43845 S49180 S58084 S93798 315341bp DNA PLN 14-FEB-1995 S.cerevisiae chromosome III complete DNA sequence. chromosome. SCU20323 U20323 1041bp DNA PLN 15-FEB-1995 Saccharomyces cerevisiae ankyrin-like protein gene, complete cds. . SCVPS9 U20373 1721bp DNA PLN 16-FEB-1995 Saccharomyces cerevisiae Vps9p (VPS9) gene, complete cds. . YSCL9753 U21094 24761bp ds-DNA PLN 16-FEB-1995 Saccharomyces cerevisiae chromosome XII cosmid 9753 ...

miR-302/367/LATS2/YAP Pathway Is Essential for Prostate Tumor-Propagating Cells and Promotes the Development of Castration Resistance Researchers report that the miR-302/367 cluster, a previously identified potent pluripotency regulator, is upregulated in prostate tumors. The forced expression of the miR-302/367 cluster accelerated the in vitro and in vivo growth of prostate cancer (PCa) cells and their resistance to androgen ablation, whereas the knockdown of the miR-302/367 cluster using anti-sense RNA suppressed the incidence of formation, growth rate and endpoint weight of PCa cell tumors. [Oncogene] Abstract Colorectal Cancer Stem Cells Acquire Chemoresistance through the Upregulation of F-Box/WD Repeat-Containing Protein 7 and the Consequent Degradation of c-Myc Investigators elucidated the molecular mechanisms responsible for evading cell death in colorectal CSCs mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, they found that c-Myc expression was ...

The invention relates to modulating BimEL levels (Bcl-2-Interacting Mediator of cell death, Extra Long isoform) to sensitize cancer cells to cell death or apoptosis. In certain embodiments, the invention relates to increasing BimEL levels. In certain embodiments, the invention relates to inhibitors of at least one of β-TrCP1/2 or RSK1/2 proteins that sensitize tumor cells to chemotherapy-induced death or apoptosis. Additionally, the invention relates to cancer therapies, diagnostics, and methods for identifying novel drugs or drug candidates for increasing BimEL levels.

Dual phosphorylation of S32 and S36 in the TrCP1-binding motif of NF-kappa-B inhibitor alpha (NFKBIA) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation ...

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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.

Eiraku M, Hirata Y, Takeshima H, Hirano T, Kengaku M. Delta/notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like repeat-containing protein targeted to dendrites of developing and adult central nervous system neurons ...

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Date: Wed, 10 Sep 1997 16:49:41 +0100 (BST) From: Dave Carter ,[email protected], To: marduk ,[email protected], cc: WWW-HTML Mailing List ,[email protected], In-Reply-To: ,[email protected], Message-ID: ,Pine.SOL.3.96.970910164556.5084F-100000@cass40, Subject: Re: HTML4.0 draft: comments re: inclusion of frames (fwd) On Wed, 10 Sep 1997, marduk wrote: , , MZ writes: , , I completely disagree. Personally I think the 3.0 proposal was bloated , , with more worthless crap that 3.2 or 4.0. , , I just joined this list, so I dont knwo whther this has been discussed , before, but I see the 4.0 proposal as doing exactly what I felt the 3.2 , proposal did, mainly to keep up with what has already been implemented by , Netscape and Microsoft and generally already accepted as standard. The only thing I would disagree with here is the notion that implementing what Netscape and Microsoft want is in any sense keeping up. Keeping up implies with something worthwhile. , , It ...

Scott Boras had some words for the New York Mets, Chicago Cubs and Houston Astros, and they were far from kind. And he also backed the Tampa Bay Rays desire for a new ballpark. On the third day of the ...

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The transcription factor NF-E2-related factor 2 (Nrf2) is a master regulator of a genetic program, termed the phase 2 response, that controls redox homeostasis and participates in multiple aspects of physiology and pathology. Nrf2 protein stability is regulated by two E3 ubiquitin ligase adaptors, Keap1 and ß-TrCP, the latter of which was only recently reported. Here, two-dimensional (2D) gel electrophoresis and site-directed mutagenesis allowed us to identify two serines of Nrf2 that are phosphorylated by glycogen synthase kinase 3ß (GSK-3ß) in the sequence DSGISL. Nuclear magnetic resonance studies defined key residues of this phosphosequence involved in docking to the WD40 propeller of ß-TrCP, through electrostatic and hydrophobic interactions. We also identified three arginine residues of ß-TrCP that participate in Nrf2 docking. Intraperitoneal injection of the GSK-3 inhibitor SB216763 led to increased Nrf2 and heme oxygenase-1 levels in liver and hippocampus. Moreover, mice with ...

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WDR85 Full-Length MS Protein Standard (NP_620133), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. WDR85 is a WD repeat-containing protein that plays a role in the first step of diphthamide biosynthesis (Carette et al., 2009 )

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Forwarded message ---------- Date: Tue, 14 Jun 1994 19:58:00 +0800 (WST) From: Philip OBrien ,obrien at csuvax1, To: methodsandreagents at net.bio.net Subject: Returned mail: User unknown (fwd) ---------- Forwarded message ---------- Date: Tue, 14 Jun 94 19:54:55 +0800 From: Mail Delivery Subsystem ,MAILER-DAEMON at csuvax1, To: postmaster at csuvax1, obrien at csuvax1 Subject: Returned mail: User unknown ----- Transcript of session follows ----- 550 methods-and at csuvax1... User unknown ----- Unsent message follows ----- Received: by csuvax1.murdoch.edu.au (5.65/1.34) id AA24084; Tue, 14 Jun 94 19:54:55 +0800 Date: Tue, 14 Jun 1994 19:45:50 +0800 (WST) From: Philip OBrien ,obrien at csuvax1, Subject: DEGENERATE PCR To: methods-and at csuvax1 Message-Id: ,Pine.3.87.9406141950.A23910-0100000 at csuvax1, Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Dear netters In order to clone pectic enzyme genes from fungi we have identified conserved regions within the genes (from amino acid ...

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7 - seems like a great deal for Heyman to me actually. His getting the first scoop time and time again will keep him employed until the day Boras decides hed rather own his own island that dupe desperate GMs. Meanwhile I doubt that propaganda from Heyman actually gets one more dollar for a Boras client. Fans will eat it up, but nobody working in a front office is getting their information from CBS Sports ...

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