The F-box protein family
Tóm tắt
The F-box is a protein motif of approximately 50 amino acids that functions as a site of protein-protein interaction. F-box proteins were first characterized as components of SCF ubiquitin-ligase complexes (named after their main components, Skp I, Cullin, and an F-box protein), in which they bind substrates for ubiquitin-mediated proteolysis. The F-box motif links the F-box protein to other components of the SCF complex by binding the core SCF component Skp I. F-box proteins have more recently been discovered to function in non-SCF protein complexes in a variety of cellular functions. There are 11 F-box proteins in budding yeast, 326 predicted in Caenorhabditis elegans, 22 in Drosophila, and at least 38 in humans. F-box proteins often include additional carboxy-terminal motifs capable of protein-protein interaction; the most common secondary motifs in yeast and human F-box proteins are WD repeats and leucine-rich repeats, both of which have been found to bind phosphorylated substrates to the SCF complex. The majority of F-box proteins have other associated motifs, and the functions of most of these proteins have not yet been defined.
Tài liệu tham khảo
Kumar A, Paietta JV: The sulfur controller-2 negative regulatory gene of Neurospora crassa encodes a protein with beta-transducin repeats. Proc Natl Acad Sci USA. 1995, 92: 3343-3347. The first description of the protein region that became known as the F box.
Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ: SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996, 86: 263-274. 10.1016/S0092-8674(00)80098-7. This work was the first to recognize the F-box as a widespread protein motif,and demonstrated that the F-box bound to the Skp1 protein.
Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M: Identification of a family of human F-box proteins. Curr Biol. 1999, 9: 1177-1179. 10.1016/S0960-9822(00)80020-2. This paper extended the number of known F-box proteins in humans and demonstrated that F-box proteins without WD or LRR motifs can bind to SCF components in vivo.
Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW: A family of mammalian F-box proteins. Curr Biol. 1999, 9: 1180-1182. 10.1016/S0960-9822(00)80021-4. Extended the number of known F-box proteins in humans and mice.
Clifford R, Lee M-H, Nayak S, Ohmachi M, Giorgini F, Schedl T: FOG-2, a novel F-box containing protein, associates with the GLD-1 RNA binding protein to direct male sex determination in the C. elegans hermaphrodite germline. Development. 2000, Demonstrates that the F-box protein FOG-2 functions in a protein complex with the RNA binding protein GLD-1 to repress tra-2mRNA translation.,
ISREC ProfileScan Server. This site can be used to search both the Pfam and Prosite databases for F-box motifs., [http://www.isrec.isb-sib.ch/software/PFSCAN_form.html]
Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW: F-Box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell. 1997, 91: 209-219. 10.1016/S0092-8674(00)80403-1. In this seminal paper and the following one, the authors reconstituted active SCF E3 complexes with purified components thereby demonstrating the biochemical action of the complex and the subunit interaction.
Feldman RMR, Correll CC, Kaplan KB, Deshaies RJ: A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell. 1997, 91: 221-230. 10.1016/S0092-8674(00)80404-3. See [7].
Tyers M, Jorgensen P: Proteolysis and the cell cycle: with this RING I do thee destroy. Curr Opin Genet Dev. 2000, 10: 54-64. 10.1016/S0959-437X(99)00049-0. Provides an overview of SCF and APC complexes.
Deshaies RJ: SCF and Cullin/Ring H2-based ubiquitin ligases. Annu Rev Cell Dev Biol. 1999, 15: 435-467. 10.1146/annurev.cellbio.15.1.435. A detailed review of SCF ubiquitin-ligase complexes.
Craig KL, Tyers M: The F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction. Prog Biophys Mol Biol. 1999, 72: 299-328. 10.1016/S0079-6107(99)00010-3. A second detailed review of SCF ubiquitin-ligase complexes.
Hershko A, Ciechanover A: The ubiquitin system. Annu Rev Biochem. 1998, 67: 425-479. 10.1146/annurev.biochem.67.1.425. A detailed review of the ubiquitin proteolytic pathway.
Russell ID, Grancell AS, Sorger PK: The unstable F-box protein p58-Ctf13 forms the structural core of the CBF3 kineto-chore complex. J Cell Biol. 1999, 145: 933-950. 10.1083/jcb.145.5.933. This work provides evidence that the F-box motif of Ctf13 is required for binding Skp1 and that the CBF3 complex assembles around Ctf13.
Kaplan KB, Hyman AA, Sorger PK: Regulating the yeast kineto-chore by ubiquitin-dependent degradation and Skp1p-mediated phosphorylation. Cell. 1997, 91: 491-500. 10.1016/S0092-8674(00)80435-3. Describes Skp1 binding to the kinetochore protein Ctf13 and promoting the activating-phosphorylation of Ctf13.
Doheny KF, Sorger PK, Hyman AA, Tugendreich S, Spencer F, Hieter P: Identification of essential components of the S. cerevisiae kinetochore. Cell. 1993, 73: 761-774. 10.1016/0092-8674(93)90255-O. This paper describes the Ctf13 loss-of-function phenotype.
Shilatifard A: Factors regulating the transcriptional elongation activity of RNA polymerase II. FASEB J. 1998, 12: 1437-1446. A review of RNA polymerase II transcriptional elongation factors, including the F-box protein Elongin A.
Aso T, Haque D, Barstead RJ, Conaway RC, Conaway JW: The inducible elongin A elongation activation domain: structure, function and interaction with the elongin BC complex. EMBO J. 1996, 15: 5557-5566. This work and [18] found that the smallest human or yeast [18] Elongin A region sufficient for binding Elongin C contained the F-box motif.
Koth CM, Botuyan MV, Moreland RJ, Jansma DB, Conaway JW, Conaway RC, Chazin WJ, Friesen JD, Arrowsmith CH, Edwards AM: Elongin from Saccharomyces cerevisiae. J Biol Chem. 2000, 275: 11174-11180. 10.1074/jbc.275.15.11174. See [17]
Jan E, Motzny CK, Graves LE, Goodwin EB: The STAR protein, GLD-1, is a translational regulator of sexual identity in Caenorhabditis elegans. EMBO J. 1999, 18: 258-269. 10.1093/emboj/18.1.258. Shows that GLD-1 translationally represses tra-2 by binding the tra-2 3' UTR.
Kong M, Barnes EA, Ollendorff V, Donoghue DJ: Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin-cyclin interaction. EMBO J. 2000, 19: 1378-1388. 10.1093/emboj/19.6.1378. Demonstrates that cyclin F binds cyclin B through a cyclin box-CRS interaction.
Zhou P, Howley PM: Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases. Mol Cell. 1998, 2: 571-580. 10.1016/S1097-2765(00)80156-2. This study represents the first demonstration that F-box proteins are unstable proteins.
Galan JM, Peter M: Ubiquitin-dependent degradation of multiple F-box proteins by an autocatalytic mechanism. Proc Natl Acad Sci USA. 1999, 96: 9124-9129. 10.1073/pnas.96.16.9124. This paper shows that ubiquitination of the F-box protein Cdc4 and Grr1 requires all the core components of the SCF and an intact F box.
Rouillon A, Barbey R, Patton EE, Tyers M, Thomas D: Feedback-regulated degradation of the transcriptional activator Met4 is triggered by the SCF(Met30) complex. EMBO J. 2000, 19: 282-294. 10.1093/emboj/19.2.282. Demonstrates that Met30 can be degraded in an F-box-independent manner.
Zhang H, Kobayashi R, Galaktionov K, Beach D: p19-Skp1 and p45-Skp2 are essential elements of the cyclin A-CDK2 S phase kinase. Cell. 1995, 82: 915-925. 10.1016/0092-8674(95)90271-6. Describes the cloning of Skp1 and Skp2 as cyclin-A-interacting proteins.
Carrano AC, Eytan E, Hershko A, Pagano M: SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat Cell Biol. 1999, 1: 193-199. 10.1038/12013. This work and [39,40] demonstrate that the SCF Skp2 complex targets the degradation of p27Kip1in vitro and in vivo.
Yam CH, Ng RW, Siu WY, Lau AW, Poon RY: Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2. Mol Cell Biol. 1999, 19: 635-645. Identifies the phosphorylation site in Skp2 targeted by cyclin A.
Spiegelman VS, Slaga TJ, Pagano M, Minamoto T, Ronai Z, Fuchs SY: Wnt/beta-catenin signaling induces the expression and activity of betaTrCP ubiquitin ligase receptor. Mol Cell. 2000, 5: 877-882. 10.1016/S1097-2765(00)80327-5. Shows that ß-catenin induces a stabilization of ß-Trcp mRNA,suggesting that a negative feedback loop regulation may control the ß-catenin pathway.
Li FN, Johnston M: Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle. EMBO J. 1997, 16: 5629-5638. 10.1093/emboj/16.18.5629. This work demonstrates that the ability of Grr1 to bind the SCF component Skp1 is upregulated in cells grown in the presence of glucose.
European Bioinformatics Institute Proteome Analysis. The InterPro project catalogs proteomes by analyzing protein motifs. Links from this page can produce lists of all of the cataloged F-box proteins in an organism, with accompanying figures of the motifs in each protein., [http://www.ebi.ac.uk/proteome/index.html]
Pfam entry: F-box. This page provides links to the alignments used to generate the Pfam F-box search algorithm., [http://pfam.wustl.edu/cgi-bin/getdesc?name=F-box]
GenBank. Database of DNA and protein sequences., [http://www.ncbi.nlm.nih.gov/Genbank/GenbankOverview.html]
Samach A, Klenz JE, Kohalmi SE, Risseeuw E, Haughn GW, Crosby WL: The UNUSUAL FLORAL ORGANS gene of Arabidopsis thaliana is an F-box protein required for normal patterning and growth in the floral meristem. Plant J. 1999, 20: 433-445. 10.1046/j.1365-313X.1999.00617.x. Demonstrates that the F-box protein UFO, which functions in flower development, interacts with Skp1-related proteins.
Ingram GC, Doyle S, Carpenter R, Schultz EA, Simon R, Coen ES: Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirrhinum. EMBO J. 1997, 16: 6521-6534. 10.1093/emboj/16.21.6521. Demonstrates that the F-box protein FIM, an ortholog of UFO, interacts with Skp1-related proteins.
Kipreos ET, Gohel SP, Hedgecock EM: The C. elegans F-box/WD-repeat protein LIN-23 functions to limit cell division during development. Development. 2000, 127: 5071-5082. Shows that the F-box protein LIN-23 functions cell autonomously to limit cell division in C.elegans.
Wojcik EJ, Glover DM, Hays TS: The SCF ubiquitin ligase protein Slimb regulates centrosome duplication in Drosophila. Curr Biol. 2000, 10: 1131-1134. 10.1016/S0960-9822(00)00703-X. Found that mutants of the slimb gene,encoding an F-box protein, have centrosome overduplication.
Kaiser P, Flick K, Wittenberg C, Reed SI: Regulation of transcription by ubiquitination without proteolysis: Cdc34/ SCF(Met30)-mediated inactivation of the transcription factor Met4. Cell. 2000, 102: 303-314. 10.1016/S0092-8674(00)00036-2. Demonstrates that SCFMet30-mediated ubiqutination of Met4 inhibits Met4 transcriptional activity but does not lead to Met4 degradation.
Meimoun A, Holtzman T, Weissman Z, McBride HJ, Stillman DJ, Fink GR, Kornitzer D: Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCF(CDC4) ubiquitin-ligase complex. Mol Biol Cell. 2000, 11: 915-927. This paper demonstrates that the transcription factor Gcn4 is targetedfor degradation by SCFCdc4.
Nakayama K, Nagahama H, Minamishima YA, Matsumoto M, Nakamichi I, Kitagawa K, Shirane M, Tsunematsu R, Tsukiyama T, Ishida N, et al: Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication. EMBO J. 2000, 19: 2069-2081. 10.1093/emboj/19.9.2069. Demonstration that mice lacking the F-box protein Skp2 are viable but in certain tissues have an accumulation of cyclin E and p27Kip1 as well as centrosome overduplication.
Sutterluty H, Chatelain E, Marti A, Wirbelauer C, Senften M, Muller U, Krek W: p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells. Nat Cell Biol. 1999, 1: 207-214. 10.1038/12027. See [250]
Tsvetkov LM, Yeh KH, Lee SJ, Sun H, Zhang H: p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27. Curr Biol. 1999, 9: 661-664. 10.1016/S0960-9822(99)80290-5. See [25]