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SKP2  -  putative SCF ubiquitin ligase complex...

Saccharomyces cerevisiae S288c

Synonyms: F-box protein SKP2, N0376, YNL311C
 
 
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High impact information on SKP2

  • The F box protein Dsg1/Mdm30 is a transcriptional coactivator that stimulates Gal4 turnover and cotranscriptional mRNA processing [1].
  • A large number of proteins contain the F-box motif and are thereby implicated in the ubiquitin pathway [2].
  • They bind the SCF constant catalytic core by means of the F-box motif interacting with Skp1, and they bind substrates through their variable protein-protein interaction domains [3].
  • We identify candidate centrosomal F-box proteins, suggesting that distinct SCF complexes may direct proteolysis of factors mediating multiple steps in the centrosome cycle [4].
  • Skp1 binds a motif called the F-box and in turn F-box proteins appear to recruit specific substrates for ubiquitination [5].
 

Biological context of SKP2

  • A vast array of F-box proteins have been revealed by genome sequencing projects, and the early returns from genetic analysis in several organisms promise that F-box proteins will participate in the regulation of many processes, including cell division, transcription, signal transduction and development [6].
  • Many key activators and inhibitors of cell division are targeted for degradation by a recently described family of E3 ubiquitin protein ligases termed Skp1-Cdc53-F-box protein (SCF) complexes [7].
  • SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box [2].
  • Our data, in combination with previously published results, also provide evidence for distinct SCF complexes in vivo and support the idea that their F-box subunits mediate SCF substrate specificity [8].
  • The unstable F-box protein p58-Ctf13 forms the structural core of the CBF3 kinetochore complex [9].
 

Anatomical context of SKP2

 

Associations of SKP2 with chemical compounds

 

Physical interactions of SKP2

  • We show that the Ho degradation pathway involving UBC3(Cdc34) goes through the Skp1/Cdc53/F-box (SCF) ubiquitin ligase complex and identify a F-box protein, Yml088w, that is required for Ho degradation [18].
  • Skp1p also binds F-box proteins in a number of non-SCF complexes [19].
  • Skp1p and the F-box protein Rcy1p form a non-SCF complex involved in recycling of the SNARE Snc1p in yeast [20].
  • Overexpression of Arabidopsis thaliana SKP1 homologues in yeast inactivates the Mig1 repressor by destabilising the F-box protein Grr1 [21].
 

Enzymatic interactions of SKP2

  • The autoubiquitination of each F-box was in some cases catalyzed only by Cdc34, and in other cases preferentially catalyzed by Ubc4 [22].
 

Regulatory relationships of SKP2

  • Although a role for the F-box protein Mdm30 in regulating the stability of Fzo1 has been proposed, the molecular basis for the regulation of the fission to fusion ratio of mitochondria remains unknown [23].
 

Other interactions of SKP2

  • The F-box motif is not essential for Mfb1p-mediated mitochondrial network formation [24].
  • Through mass spectrometric analysis of Cdc53 associated proteins, we have identified three novel F-box proteins that appear to participate in SCF-like complexes [7].
  • Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and F-Box protein Grr1p are required for transcriptional induction of the AGP1 gene, which encodes a broad-specificity amino acid permease [25].
  • Here we show that the F-box protein Rcy1p is required for recycling of the v-SNARE Snc1p in Saccharomyces cerevisiae [20].
  • Unlike the case for F-box proteins that are known to participate in SCF complexes, degradation of Rcy1p required neither its F box nor functional 26S proteasomes or other SCF core subunits [20].
 

Analytical, diagnostic and therapeutic context of SKP2

References

  1. The F box protein Dsg1/Mdm30 is a transcriptional coactivator that stimulates Gal4 turnover and cotranscriptional mRNA processing. Muratani, M., Kung, C., Shokat, K.M., Tansey, W.P. Cell (2005) [Pubmed]
  2. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Bai, C., Sen, P., Hofmann, K., Ma, L., Goebl, M., Harper, J.W., Elledge, S.J. Cell (1996) [Pubmed]
  3. Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex. Schulman, B.A., Carrano, A.C., Jeffrey, P.D., Bowen, Z., Kinnucan, E.R., Finnin, M.S., Elledge, S.J., Harper, J.W., Pagano, M., Pavletich, N.P. Nature (2000) [Pubmed]
  4. Components of an SCF ubiquitin ligase localize to the centrosome and regulate the centrosome duplication cycle. Freed, E., Lacey, K.R., Huie, P., Lyapina, S.A., Deshaies, R.J., Stearns, T., Jackson, P.K. Genes Dev. (1999) [Pubmed]
  5. Cdc53 is a scaffold protein for multiple Cdc34/Skp1/F-box proteincomplexes that regulate cell division and methionine biosynthesis in yeast. Patton, E.E., Willems, A.R., Sa, D., Kuras, L., Thomas, D., Craig, K.L., Tyers, M. Genes Dev. (1998) [Pubmed]
  6. Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis. Patton, E.E., Willems, A.R., Tyers, M. Trends Genet. (1998) [Pubmed]
  7. SCF ubiquitin protein ligases and phosphorylation-dependent proteolysis. Willems, A.R., Goh, T., Taylor, L., Chernushevich, I., Shevchenko, A., Tyers, M. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (1999) [Pubmed]
  8. Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1. Kaiser, P., Sia, R.A., Bardes, E.G., Lew, D.J., Reed, S.I. Genes Dev. (1998) [Pubmed]
  9. The unstable F-box protein p58-Ctf13 forms the structural core of the CBF3 kinetochore complex. Russell, I.D., Grancell, A.S., Sorger, P.K. J. Cell Biol. (1999) [Pubmed]
  10. The F-box protein Rcy1p is involved in endocytic membrane traffic and recycling out of an early endosome in Saccharomyces cerevisiae. Wiederkehr, A., Avaro, S., Prescianotto-Baschong, C., Haguenauer-Tsapis, R., Riezman, H. J. Cell Biol. (2000) [Pubmed]
  11. Mdm30 is an F-box protein required for maintenance of fusion-competent mitochondria in yeast. Fritz, S., Weinbach, N., Westermann, B. Mol. Biol. Cell (2003) [Pubmed]
  12. Ypt31/32 GTPases and their novel F-box effector protein Rcy1 regulate protein recycling. Chen, S.H., Chen, S., Tokarev, A.A., Liu, F., Jedd, G., Segev, N. Mol. Biol. Cell (2005) [Pubmed]
  13. F-box protein Grr1 interacts with phosphorylated targets via the cationic surface of its leucine-rich repeat. Hsiung, Y.G., Chang, H.C., Pellequer, J.L., La Valle, R., Lanker, S., Wittenberg, C. Mol. Cell. Biol. (2001) [Pubmed]
  14. Grr1-dependent inactivation of Mth1 mediates glucose-induced dissociation of Rgt1 from HXT gene promoters. Flick, K.M., Spielewoy, N., Kalashnikova, T.I., Guaderrama, M., Zhu, Q., Chang, H.C., Wittenberg, C. Mol. Biol. Cell (2003) [Pubmed]
  15. Null mutation of AtCUL1 causes arrest in early embryogenesis in Arabidopsis. Shen, W.H., Parmentier, Y., Hellmann, H., Lechner, E., Dong, A., Masson, J., Granier, F., Lepiniec, L., Estelle, M., Genschik, P. Mol. Biol. Cell (2002) [Pubmed]
  16. Proteasome- and SCF-dependent degradation of yeast adenine deaminase upon transition from proliferation to quiescence requires a new F-box protein named Saf1p. Escusa, S., Camblong, J., Galan, J.M., Pinson, B., Daignan-Fornier, B. Mol. Microbiol. (2006) [Pubmed]
  17. Identification of F-box proteins that are involved in resistance to methylmercury in Saccharomyces cerevisiae. Hwang, G.W., Ishida, Y., Naganuma, A. FEBS Lett. (2006) [Pubmed]
  18. Functions of the DNA damage response pathway target Ho endonuclease of yeast for degradation via the ubiquitin-26S proteasome system. Kaplun, L., Ivantsiv, Y., Kornitzer, D., Raveh, D. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. Skp1p regulates soi3p/rav1p association with endosomal membranes but is not required for vacuolar ATPase assembly. Brace, E.J., Parkinson, L.P., Fuller, R.S. Eukaryotic Cell (2006) [Pubmed]
  20. Skp1p and the F-box protein Rcy1p form a non-SCF complex involved in recycling of the SNARE Snc1p in yeast. Galan, J.M., Wiederkehr, A., Seol, J.H., Haguenauer-Tsapis, R., Deshaies, R.J., Riezman, H., Peter, M. Mol. Cell. Biol. (2001) [Pubmed]
  21. Overexpression of Arabidopsis thaliana SKP1 homologues in yeast inactivates the Mig1 repressor by destabilising the F-box protein Grr1. Schouten, J., de Kam, R.J., Fetter, K., Hoge, J.H. Mol. Gen. Genet. (2000) [Pubmed]
  22. Functional interaction of 13 yeast SCF complexes with a set of yeast E2 enzymes in vitro. Kus, B.M., Caldon, C.E., Andorn-Broza, R., Edwards, A.M. Proteins (2004) [Pubmed]
  23. Instability of the mitofusin Fzo1 regulates mitochondrial morphology during the mating response of the yeast Saccharomyces cerevisiae. Neutzner, A., Youle, R.J. J. Biol. Chem. (2005) [Pubmed]
  24. The novel F-box protein Mfb1p regulates mitochondrial connectivity and exhibits asymmetric localization in yeast. Kondo-Okamoto, N., Ohkuni, K., Kitagawa, K., McCaffery, J.M., Shaw, J.M., Okamoto, K. Mol. Biol. Cell (2006) [Pubmed]
  25. Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and F-Box protein Grr1p are required for transcriptional induction of the AGP1 gene, which encodes a broad-specificity amino acid permease. Iraqui, I., Vissers, S., Bernard, F., de Craene, J.O., Boles, E., Urrestarazu, A., André, B. Mol. Cell. Biol. (1999) [Pubmed]
  26. An additional role for the F-box motif: gene regulation within the Neurospora crassa sulfur control network. Kumar, A., Paietta, J.V. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  27. Skp1 and the F-box protein Pof6 are essential for cell separation in fission yeast. Hermand, D., Bamps, S., Tafforeau, L., Vandenhaute, J., Mäkelä, T.P. J. Biol. Chem. (2003) [Pubmed]
 
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