|
|
|
Vol. 13, No. 3, pp. 284-294, February 1, 1999
B
by the F-box protein Slimb/
-TrCP
1 Department of Molecular Biology and Oncology,
2 Center for Developmental Biology, University of Texas
Southwestern Medical Center, Dallas, Texas 75235-9148 USA
Signal-induced phosphorylation of I
B
targets this inhibitor of
NF-
B for ubiquitination and subsequent degradation, thus allowing
NF-
B to enter the nucleus to turn on its target genes. We report
here the identification of an I
B-ubiquitin (Ub) ligase complex
containing the F-box/WD40-repeat protein,
-TrCP, a
vertebrate homolog of Drosophila Slimb.
-TrCP binds to
I
B
only when the latter is specifically phosphorylated by an
I
B kinase complex. Moreover, immunopurified
-TrCP ubiquitinates
phosphorylated I
B
at specific lysines in the presence of
Ub-activating (E1) and -conjugating (Ubch5) enzymes. A
-TrCP mutant
lacking the F-box inhibits the signal-induced degradation of I
B
and subsequent activation of NF-
B-dependent transcription.
Furthermore, Drosophila embryos deficient in slimb fail
to activate twist and snail, two genes known to be
regulated by the NF-
B homolog, Dorsal. These biochemical and genetic
data strongly suggest that Slimb/
-TrCP is the
specificity determinant for the signal-induced ubiquitination of I
B
.
[Key Words:
Phosphorylation; NF-
B; I
B; ubiquitin; SCF; Slimb;
-TrCP]
This article has been cited by other articles:
![]() |
S. Sun, Y. Tang, X. Lou, L. Zhu, K. Yang, B. Zhang, H. Shi, and C. Wang UXT is a novel and essential cofactor in the NF-{kappa}B transcriptional enhanceosome J. Cell Biol., July 10, 2007; 178(2): 231 - 244. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Pan and B. Wang A Novel Protein-processing Domain in Gli2 and Gli3 Differentially Blocks Complete Protein Degradation by the Proteasome J. Biol. Chem., April 13, 2007; 282(15): 10846 - 10852. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Butticaz, O. Michielin, J. Wyniger, A. Telenti, and S. Rothenberger Silencing of both {beta}-TrCP1 and HOS ({beta}-TrCP2) Is Required To Suppress Human Immunodeficiency Virus Type 1 Vpu-Mediated CD4 Down-Modulation J. Virol., February 1, 2007; 81(3): 1502 - 1505. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. H. Ki, M. J. Choi, C. H. Lee, and S. G. Kim G{alpha}12 Specifically Regulates COX-2 Induction by Sphingosine 1-Phosphate: ROLE FOR JNK-DEPENDENT UBIQUITINATION AND DEGRADATION OF I{kappa}B{alpha} J. Biol. Chem., January 19, 2007; 282(3): 1938 - 1947. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Yang, W. Zhang, P. M. Evans, X. Chen, X. He, and C. Liu Adenomatous Polyposis Coli (APC) Differentially Regulates beta-Catenin Phosphorylation and Ubiquitination in Colon Cancer Cells J. Biol. Chem., June 30, 2006; 281(26): 17751 - 17757. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Pan, C. B. Bai, A. L. Joyner, and B. Wang Sonic hedgehog Signaling Regulates Gli2 Transcriptional Activity by Suppressing Its Processing and Degradation. Mol. Cell. Biol., May 1, 2006; 26(9): 3365 - 3377. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. W. Wang, N. S. Tan, B. Ho, and J. L. Ding Evidence for the ancient origin of the NF-{kappa}B/I{kappa}B cascade: Its archaic role in pathogen infection and immunity. PNAS, March 14, 2006; 103(11): 4204 - 4209. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. G. Huntzicker, I. S. Estay, H. Zhen, L. A. Lokteva, P. K. Jackson, and A. E. Oro Dual degradation signals control Gli protein stability and tumor formation Genes & Dev., February 1, 2006; 20(3): 276 - 281. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Wang and Y. Li Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing PNAS, January 3, 2006; 103(1): 33 - 38. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. S. Collier-Hyams, V. Sloane, B. C. Batten, and A. S. Neish Cutting Edge: Bacterial Modulation of Epithelial Signaling via Changes in Neddylation of Cullin-1 J. Immunol., October 1, 2005; 175(7): 4194 - 4198. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Shirogane, J. Jin, X. L. Ang, and J. W. Harper SCF{beta}-TRCP Controls Clock-dependent Transcription via Casein Kinase 1-dependent Degradation of the Mammalian Period-1 (Per1) Proteinm J. Biol. Chem., July 22, 2005; 280(29): 26863 - 26872. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Wan, J. Huang, N. C. Jhala, E. M. Tytler, L. Yang, S. M. Vickers, Y. Tang, C. Lu, N. Wang, and X. Cao SCF{beta}-TrCP1 Controls Smad4 Protein Stability in Pancreatic Cancer Cells Am. J. Pathol., May 1, 2005; 166(5): 1379 - 1392. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Girao, P. Pereira, A. Taylor, and F. Shang Subcellular Redistribution of Components of the Ubiquitin-Proteasome Pathway during Lens Differentiation and Maturation Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1386 - 1392. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-S. Yang, C. Yu, H.-C. Chuang, C.-W. Chang, G.-D. Chang, T.-P. Yao, and H. Chen FBW2 Targets GCMa to the Ubiquitin-Proteasome Degradation System J. Biol. Chem., March 18, 2005; 280(11): 10083 - 10090. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Srinivas, D. M. Juroske, S. Kalyankrishna, D. D. Cody, R. E. Price, X.-C. Xu, R. Narayanan, N. L. Weigel, and J. M. Kurie c-Jun N-Terminal Kinase Contributes to Aberrant Retinoid Signaling in Lung Cancer Cells by Phosphorylating and Inducing Proteasomal Degradation of Retinoic Acid Receptor {alpha} Mol. Cell. Biol., February 1, 2005; 25(3): 1054 - 1069. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Ye, G. Nalepa, M. Welcker, B. M. Kessler, E. Spooner, J. Qin, S. J. Elledge, B. E. Clurman, and J. W. Harper Recognition of Phosphodegron Motifs in Human Cyclin E by the SCFFbw7 Ubiquitin Ligase J. Biol. Chem., November 26, 2004; 279(48): 50110 - 50119. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. D. Donaldson, M. A. Noureddine, P. J. Reynolds, W. Bradford, and R. J. Duronio Targeted Disruption of Drosophila Roc1b Reveals Functional Differences in the Roc Subunit of Cullin-dependent E3 Ubiquitin Ligases Mol. Biol. Cell, November 1, 2004; 15(11): 4892 - 4903. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Kudo, D. Guardavaccaro, P. G. Santamaria, R. Koyama-Nasu, E. Latres, R. Bronson, L. Yamasaki, and M. Pagano Role of F-Box Protein {beta}Trcp1 in Mammary Gland Development and Tumorigenesis Mol. Cell. Biol., September 15, 2004; 24(18): 8184 - 8194. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Khoshnan, J. Ko, E. E. Watkin, L. A. Paige, P. H. Reinhart, and P. H. Patterson Activation of the I{kappa}B Kinase Complex and Nuclear Factor-{kappa}B Contributes to Mutant Huntingtin Neurotoxicity J. Neurosci., September 15, 2004; 24(37): 7999 - 8008. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. S. Hayden and S. Ghosh Signaling to NF-{kappa}B Genes & Dev., September 15, 2004; 18(18): 2195 - 2224. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-M. Hsu, Y.-C. G. Lee, C.-T. R. Yu, and C.-Y. F. Huang Fbx7 Functions in the SCF Complex Regulating Cdk1-Cyclin B-phosphorylated Hepatoma Up-regulated Protein (HURP) Proteolysis by a Proline-rich Region J. Biol. Chem., July 30, 2004; 279(31): 32592 - 32602. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. O'Connor, S. D. Shumway, I. J. Amanna, C. E. Hayes, and S. Miyamoto Regulation of Constitutive p50/c-Rel Activity via Proteasome Inhibitor-Resistant I{kappa}B{alpha} Degradation in B Cells Mol. Cell. Biol., June 1, 2004; 24(11): 4895 - 4908. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Li, K. G. Suresh Kumar, W. Tang, V. S. Spiegelman, and S. Y. Fuchs Negative Regulation of Prolactin Receptor Stability and Signaling Mediated by SCF{beta}-TrCP E3 Ubiquitin Ligase Mol. Cell. Biol., May 1, 2004; 24(9): 4038 - 4048. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Besnard-Guerin, N. Belaidouni, I. Lassot, E. Segeral, A. Jobart, C. Marchal, and R. Benarous HIV-1 Vpu Sequesters {beta}-Transducin Repeat-containing Protein ({beta}TrCP) in the Cytoplasm and Provokes the Accumulation of {beta}-Catenin and Other SCF{beta}TrCP Substrates J. Biol. Chem., January 2, 2004; 279(1): 788 - 795. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Wang, N. Adhikari, Q. Li, Z. Guan, and J. L. Hall The Role of {beta}-Transducin Repeat-Containing Protein ({beta}-TrCP) in the Regulation of NF-{kappa}B in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 85 - 90. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Jin, T. Shirogane, L. Xu, G. Nalepa, J. Qin, S. J. Elledge, and J. W. Harper SCF{beta}-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase Genes & Dev., December 15, 2003; 17(24): 3062 - 3074. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Tang, O. A. Pavlish, V. S. Spiegelman, A. A. Parkhitko, and S. Y. Fuchs Interaction of Epstein-Barr Virus Latent Membrane Protein 1 with SCFHOS/{beta}-TrCP E3 Ubiquitin Ligase Regulates Extent of NF-{kappa}B Activation J. Biol. Chem., December 5, 2003; 278(49): 48942 - 48949. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Mantovani and L. Banks Regulation of the Discs Large Tumor Suppressor by a Phosphorylation-dependent Interaction with the {beta}-TrCP Ubiquitin Ligase Receptor J. Biol. Chem., October 24, 2003; 278(43): 42477 - 42486. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Kishore, C. Sommers, S. Mathialagan, J. Guzova, M. Yao, S. Hauser, K. Huynh, S. Bonar, C. Mielke, L. Albee, et al. A Selective IKK-2 Inhibitor Blocks NF-{kappa}B-dependent Gene Expression in Interleukin-1{beta}-stimulated Synovial Fibroblasts J. Biol. Chem., August 29, 2003; 278(35): 32861 - 32871. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. De Bosscher, W. Vanden Berghe, and G. Haegeman The Interplay between the Glucocorticoid Receptor and Nuclear Factor-{kappa}B or Activator Protein-1: Molecular Mechanisms for Gene Repression Endocr. Rev., August 1, 2003; 24(4): 488 - 522. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Nakayama, S. Hatakeyama, S.-i. Maruyama, A. Kikuchi, K. Onoe, R. A. Good, and K. I. Nakayama Impaired degradation of inhibitory subunit of NF-{kappa}B (I{kappa}B) and {beta}-catenin as a result of targeted disruption of the {beta}-TrCP1 gene PNAS, July 22, 2003; 100(15): 8752 - 8757. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Lee, K. Amanai, A. Shearn, and J. E. Treisman The ubiquitin ligase Hyperplastic discs negatively regulates hedgehog and decapentaplegic expression by independent mechanisms Development, March 14, 2003; 129(24): 5697 - 5706. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. S. Spiegelman, W. Tang, A. M. Chan, M. Igarashi, S. A. Aaronson, D. A. Sassoon, M. Katoh, T. J. Slaga, and S. Y. Fuchs Induction of Homologue of Slimb Ubiquitin Ligase Receptor by Mitogen Signaling J. Biol. Chem., September 20, 2002; 277(39): 36624 - 36630. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Jiang Degrading Ci: who is Cul-pable? Genes & Dev., September 15, 2002; 16(18): 2315 - 2321. [Full Text] [PDF] |
||||
![]() |
C.-Y. Ou, Y.-F. Lin, Y.-J. Chen, and C.-T. Chien Distinct protein degradation mechanisms mediated by Cul1 and Cul3 controlling Ci stability in Drosophila eye development Genes & Dev., September 15, 2002; 16(18): 2403 - 2414. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. S. Collier-Hyams, H. Zeng, J. Sun, A. D. Tomlinson, Z. Q. Bao, H. Chen, J. L. Madara, K. Orth, and A. S. Neish Cutting Edge: Salmonella AvrA Effector Inhibits the Key Proinflammatory, Anti-Apoptotic NF-{kappa}B Pathway J. Immunol., September 15, 2002; 169(6): 2846 - 2850. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. T. Huang, S. L. Feinberg, S. Suryanarayanan, and S. Miyamoto The Zinc Finger Domain of NEMO Is Selectively Required for NF-{kappa}B Activation by UV Radiation and Topoisomerase Inhibitors Mol. Cell. Biol., August 15, 2002; 22(16): 5813 - 5825. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Li, J. C. Ruiz, and K. T. Chun CUL-4A Is Critical for Early Embryonic Development Mol. Cell. Biol., July 15, 2002; 22(14): 4997 - 5005. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Kanayama, J.-i. Inoue, Y. Sugita-Konishi, M. Shimizu, and Y. Miyamoto Oxidation of Ikappa Balpha at Methionine 45 Is One Cause of Taurine Chloramine-induced Inhibition of NF-kappa B Activation J. Biol. Chem., June 28, 2002; 277(27): 24049 - 24056. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. C. Swinney, Y.-Z. Xu, L. E. Scarafia, I. Lee, A. Y. Mak, Q.-F. Gan, C. S. Ramesha, M. A. Mulkins, J. Dunn, O.-Y. So, et al. A Small Molecule Ubiquitination Inhibitor Blocks NF-kappa B-dependent Cytokine Expression in Cells and Rats J. Biol. Chem., June 21, 2002; 277(26): 23573 - 23581. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Kishore, Q. K. Huynh, S. Mathialagan, T. Hall, S. Rouw, D. Creely, G. Lange, J. Caroll, B. Reitz, A. Donnelly, et al. IKK-i and TBK-1 are Enzymatically Distinct from the Homologous Enzyme IKK-2. COMPARATIVE ANALYSIS OF RECOMBINANT HUMAN IKK-i, TBK-1, AND IKK-2 J. Biol. Chem., April 12, 2002; 277(16): 13840 - 13847. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Nelson, L. Paraoan, D. G. Spiller, G. J. C. Wilde, M. A. Browne, P. K. Djali, J. F. Unitt, E. Sullivan, E. Floettmann, and M. R. H. White Multi-parameter analysis of the kinetics of NF-{kappa}B signalling and transcription in single living cells J. Cell Sci., March 15, 2002; 115(6): 1137 - 1148. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Zhande, J. J. Mitchell, J. Wu, and X. J. Sun Molecular Mechanism of Insulin-Induced Degradation of Insulin Receptor Substrate 1 Mol. Cell. Biol., February 15, 2002; 22(4): 1016 - 1026. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. K. Pandey, H.-J. He, A. Chesley, M. Juhaszova, M. T. Crow, and M. Bernier Wortmannin-Sensitive Pathway Is Required for Insulin-Stimulated Phosphorylation of Inhibitor {kappa}B{alpha} Endocrinology, February 1, 2002; 143(2): 375 - 385. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Adams Development of the Proteasome Inhibitor PS-341 Oncologist, February 1, 2002; 7(1): 9 - 16. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. T.H. Yeh Ubiquitin, Proteasome, and Restenosis: A Brave New World for Cardiovascular Research Circulation, January 29, 2002; 105(4): 408 - 410. [Full Text] [PDF] |
||||
![]() |
C. Boutell, S. Sadis, and R. D. Everett Herpes Simplex Virus Type 1 Immediate-Early Protein ICP0 and Its Isolated RING Finger Domain Act as Ubiquitin E3 Ligases In Vitro J. Virol., January 15, 2002; 76(2): 841 - 850. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Tateishi, M. Omata, K. Tanaka, and T. Chiba The NEDD8 system is essential for cell cycle progression and morphogenetic pathway in mice J. Cell Biol., November 12, 2001; 155(4): 571 - 580. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Rui, T. L. Fisher, J. Thomas, and M. F. White Regulation of Insulin/Insulin-like Growth Factor-1 Signaling by Proteasome-mediated Degradation of Insulin Receptor Substrate-2 J. Biol. Chem., October 19, 2001; 276(43): 40362 - 40367. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Silverman and T. Maniatis NF-{kappa}B signaling pathways in mammalian and insect innate immunity Genes & Dev., September 15, 2001; 15(18): 2321 - 2342. [Full Text] [PDF] |
||||
![]() |
N. Q. Fernandez, J. Grosshans, J. S. Goltz, and D. Stein Separable and redundant regulatory determinants in Cactus mediate its dorsal group dependent degradation Development, August 1, 2001; 128(15): 2963 - 2974. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Kiger Jr. and C. O'Shea Genetic Evidence for a Protein Kinase A/Cubitus Interruptus Complex That Facilitates Processing of Cubitus Interruptus in Drosophila Genetics, July 1, 2001; 158(3): 1157 - 1166. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. C. Hay, G. D. Kemp, C. Dargemont, and R. T. Hay Interaction between hnRNPA1 and I{kappa}B{alpha} Is Required for Maximal Activation of NF-{kappa}B-Dependent Transcription Mol. Cell. Biol., May 15, 2001; 21(10): 3482 - 3490. [Abstract] [Full Text] |
||||
![]() |
M. Fukuchi, T. Imamura, T. Chiba, T. Ebisawa, M. Kawabata, K. Tanaka, and K. Miyazono Ligand-dependent Degradation of Smad3 by a Ubiquitin Ligase Complex of ROC1 and Associated Proteins Mol. Biol. Cell, May 1, 2001; 12(5): 1431 - 1443. [Abstract] [Full Text] |
||||
![]() |
I. Lassot, E. Ségéral, C. Berlioz-Torrent, H. Durand, L. Groussin, T. Hai, R. Benarous, and F. Margottin-Goguet ATF4 Degradation Relies on a Phosphorylation-Dependent Interaction with the SCF{beta}TrCP Ubiquitin Ligase Mol. Cell. Biol., March 15, 2001; 21(6): 2192 - 2202. [Abstract] [Full Text] |
||||
![]() |
V. Heissmeyer, D. Krappmann, E. N. Hatada, and C. Scheidereit Shared Pathways of I{kappa}B Kinase-Induced SCF{beta}TrCP-Mediated Ubiquitination and Degradation for the NF-{kappa}B Precursor p105 and I{kappa}B{alpha} Mol. Cell. Biol., February 15, 2001; 21(4): 1024 - 1035. [Abstract] [Full Text] |
||||
![]() |
M. Furukawa, Y. Zhang, J. McCarville, T. Ohta, and Y. Xiong The CUL1 C-Terminal Sequence and ROC1 Are Required for Efficient Nuclear Accumulation, NEDD8 Modification, and Ubiquitin Ligase Activity of CUL1 Mol. Cell. Biol., November 1, 2000; 20(21): 8185 - 8197. [Abstract] [Full Text] |
||||
![]() |
|