BTRC, F-Box (Fbx) proteiini BETA-TRCP (10q24.32)

Tapasin tämän E3-ubikitiiniligaasin kun seuloin kromosomissa 22 ilmentyvien RNF- geenien luetteloa.  Yksi niistä  Ring finger proteiineista oli nimeltään ZNRF3, RNF203 ( 22q12.1)  Sinkki ja RING- finger 3. Sen sinkkisormirakenne on muotoa ZC3HC4 ja tätä sinkkisormiryhmää  kutsutaan RNF- ryhmäksi myös, koska siinä on myös  tyypillinen cross brace RING finger.  tämä sinkkisormiproteiini pystyy säätelemään inhiboiden kehityksellisiä seikkoja säätmällä alas Wnt ja Hedgehog signalointiteitä.  Sitä puolestaan ubikitinoi  F-box-perheen jäsen BETA-TRCP, joka nyt on otsikkonani.  Nämä E3-ubikitiiniligaasit  ovat fosforylaatiosta riippuvaisia ubikitinoijia.

BETA-TRCP (10q24.32)  tämä F.-box- proteiini kuuluu F-box ryhmään  Fbxs. ( F-box ryhmät ovat  Fbws, Fbls ja Fbxs).  F-box on  40 aminohapon motiivi.  E3-ubikitinaasiryhmä on SCF-tyyppinen, SKF1-cullin- F-box-  kompleksina toimiva. 
tällä E3 ubikitiiiligaasilla on runsaasti nimiä:
FWD1, FBW1A, FBXW1, bTrCP, FBXW1A, bTrCP1, betaTrCP
Mitä tietoja PubMed antaa lisää:
https://www.ncbi.nlm.nih.gov/gene/8945

Official Symbol

BTRC

Official Full Name

beta-transducin repeat containing E3 ubiquitin protein ligasep

Also known as

FWD1; FBW1A; FBXW1; bTrCP; FBXW1A; bTrCP1; betaTrCP; BETA-TRCP

Summary

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class; in addition to an F-box, this protein contains multiple WD-40 repeats. The encoded protein mediates degradation of CD4 via its interaction with HIV-1 Vpu. It has also been shown to ubiquitinate phosphorylated NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), targeting it for degradation and thus activating nuclear factor kappa-B. Alternatively spliced transcript variants have been described. A related pseudogene exists in chromosome 6. [provided by RefSeq, Mar 2012]

Expression

Ubiquitous expression in brain (RPKM 11.6), testis (RPKM 7.3) and 25 other tissues See more

• Biochim Biophys Acta Gen Subj. 2018 Oct;1862(10):2271-2280. doi: 10.1016/j.bbagen.2018.07.015. Epub 2018 Jul 18.
• β-TrCP-dependent degradation of ASK1 suppresses the induction of the apoptotic response by oxidative stress.
• Cheng R¹, Takeda K², Naguro I¹, Hatta T³, Iemura SI⁴, Natsume T³, Ichijo H⁵, Hattori K⁶. Abstract
• Apoptosis signal-regulating kinase 1 (ASK1) is a key player in the homeostatic response of many organisms. Of the many functions of ASK1, it is most well-known for its ability to induce canonical caspase 3-dependent apoptosis through the MAPK pathways in response to reactive oxygen species (ROS). As ASK1 is a regulator of apoptosis, its proper regulation is critical for the well-being of an organism. To date, several E3 ubiquitin ligases have been identified that are capable of degrading ASK1, signifying the importance of maintaining ASK1 expression levels during stress responses. ASK1 protein regulation under unstimulated conditions, however, is still largely unknown. Using tandem mass spectrometry, we have identified beta-transducin repeat containing protein (β-TrCP), an E3 ubiquitin ligase, as a novel interacting partner of ASK1 that is capable of ubiquitinating and subsequently degrading ASK1 through the ubiquitin-proteasome system (UPS). This interaction requires the seven WD domains of β-TrCP and the C-terminus of ASK1. By silencing the β-TrCP genes, we observed a significant increase in caspase 3 activity in response to oxidative stress, which could subsequently be suppressed by silencing ASK1. These findings suggest that β-TrCP is capable of suppressing oxidative stress-induced caspase 3-dependent apoptosis through suppression of ASK1, assisting in the organism's ability to maintain homeostasis in an unstable environment.
• Copyright © 2018 Elsevier B.V. All rights reserved. KEYWORDS:
• ASK1; Apoptosis; E3 ubiquitin ligase; Oxidative stress; Ubiquitin-proteasome system; β-TrCP