HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hattori, K. Articles by Nakayama, K.-i. Search for Related Content PubMed PubMed Citation Articles by Hattori, K. Articles by Nakayama, K.-i.

J Biol Chem, Vol. 274, Issue 42, 29641-29647, October 15, 1999

Molecular Dissection of the Interactions among IB, FWD1, and Skp1 Required for Ubiquitin-mediated Proteolysis of IB

Kimihiko Hattori^§, Shigetsugu Hatakeyama^§, Michiko Shirane^§, Masaki Matsumoto^§, and Kei-ichi Nakayama^§

From the  Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582 and ^§ CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan

The SCF complex containing Skp1, Cul1, and the F-box protein FWD1 (the mouse homologue of Drosophila Slimb and Xenopus -TrCP) functions as the ubiquitin ligase for IB. FWD1 associates with Skp1 through the F-box domain and also recognizes the conserved DSGXXS motif of IB. The structural requirements for the interactions of FWD1 with IB and with Skp1 have now been investigated further. The D31A mutation (but not the G33A mutation) in the DSGXXS motif of IB abolished the binding of IB to FWD1 and its subsequent ubiquitination without affecting the phosphorylation of IB. The IB mutant D31E still exhibited binding to FWD1 and underwent ubiquitination. These results suggest that, in addition to site-specific phosphorylation at Ser³² and Ser³⁶, an acidic amino acid at position 31 is required for FWD1-mediated ubiquitination of IB. Deletion analysis of Skp1 revealed that residues 61-143 of this protein are required for binding to FWD1. On the other hand, the highly conserved residues Pro¹⁴⁹, Ile¹⁶⁰, and Leu¹⁶⁴ in the F-box domain of FWD1 were dispensable for binding to Skp1. Together, these data delineate the structural requirements for the interactions among IB, FWD1, and Skp1 that underlie substrate recognition by the SCF ubiquitin ligase complex.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				S. Megy, G. Bertho, J. Gharbi-Benarous, N. Evrard-Todeschi, G. Coadou, E. Segeral, C. Iehle, E. Quemeneur, R. Benarous, and J.-P. Girault STD and TRNOESY NMR Studies on the Conformation of the Oncogenic Protein {beta}-Catenin Containing the Phosphorylated Motif DpSGXXpS Bound to the {beta}-TrCP Protein J. Biol. Chem., August 12, 2005; 280(32): 29107 - 29116. [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]

				H. Kong, J. Leebens-Mack, W. Ni, C. W. dePamphilis, and H. Ma Highly Heterogeneous Rates of Evolution in the SKP1 Gene Family in Plants and Animals: Functional and Evolutionary Implications Mol. Biol. Evol., January 1, 2004; 21(1): 117 - 128. [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]

				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]

				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]

				P. Renard, Y. Percherancier, M. Kroll, D. Thomas, J.-L. Virelizier, F. Arenzana-Seisdedos, and F. Bachelerie Inducible NF-kappa B Activation Is Permitted by Simultaneous Degradation of Nuclear Ikappa Balpha J. Biol. Chem., May 12, 2000; 275(20): 15193 - 15199. [Abstract] [Full Text] [PDF]

				N. Ishida, M. Kitagawa, S. Hatakeyama, and K.-i. Nakayama Phosphorylation at Serine 10, a Major Phosphorylation Site of p27Kip1, Increases Its Protein Stability J. Biol. Chem., August 11, 2000; 275(33): 25146 - 25154. [Abstract] [Full Text] [PDF]

				V. S. Spiegelman, P. Stavropoulos, E. Latres, M. Pagano, Z.'e. Ronai, T. J. Slaga, and S. Y. Fuchs Induction of beta -Transducin Repeat-containing Protein by JNK Signaling and Its Role in the Activation of NF-kappa B J. Biol. Chem., July 13, 2001; 276(29): 27152 - 27158. [Abstract] [Full Text] [PDF]