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Research Papers
Friedrich Miescher Institute, Basel, Switzerland.
Abstract
The LIM motif defines a double zinc finger structure found in proteins involved in cell fate determination and growth control. LIM proteins, which include LIM homeo domain, LIM kinase, focal adhesion, and LIM-only proteins, usually contain two or more LIM motifs clustered at their amino- or carboxy-terminal end. At present, the mode of action of the LIM domain is not clear. In this study we have analyzed the binding properties of LIM motifs in the cellular environment. We show that MLP, CRP, and betaCRP define a subclass of LIM-only proteins with unique dual subcellular localization in the nucleus and along actin-based filaments in the cytosol. A double MLP construct that accumulated nearly exclusively along actin filaments promoted myogenic differentiation efficiently, arguing for a functional role of cytoskeleton-associated MLP. Binding of MLP to the actin cytoskeleton is specifically attributable to its second LIM motif. An additional LIM motif potentiates binding. Potentiating LIM motifs can be interchanged, resulting in differential targeting of interacting proteins. To analyze LIM-LIM interactions in situ, this property was exploited to develop a hybrid interaction approach based on the relocalization of LIM-containing constructs to the actin cytoskeleton. These experiments revealed the existence of marked selectivity in the interactions of single LIM motifs, and among LIM domains from different LIM-homeo domain and LIM-only proteins. Furthermore, the analysis suggested that the LIM motif has two interacting interfaces. On the basis of these findings, we propose that LIM motifs function as specific adapter elements to promote the assembly and targeting of multiprotein complexes.
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S.-F. Yet, S. C. Folta, M. K. Jain, C.-M. Hsieh, K. Maemura, M. D. Layne, D. Zhang, P. B. Marria, M. Yoshizumi, M. T. Chin, et al. Molecular Cloning, Characterization, and Promoter Analysis of the Mouse Crp2/SmLim Gene. PREFERENTIAL EXPRESSION OF ITS PROMOTER IN THE VASCULAR SMOOTH MUSCLE CELLS OF TRANSGENIC MICE J. Biol. Chem., April 24, 1998; 273(17): 10530 - 10537. [Abstract] [Full Text] [PDF] |
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J. Prassler, A. Murr, S. Stocker, J. Faix, J. Murphy, and G. Marriott DdLIM Is a Cytoskeleton-associated Protein Involved in the Protrusion of Lamellipodia in Dictyostelium Mol. Biol. Cell, March 1, 1998; 9(3): 545 - 559. [Abstract] [Full Text] |
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E. Cuppen, H. Gerrits, B. Pepers, B. Wieringa, and W. Hendriks PDZ Motifs in PTP-BL and RIL Bind to Internal Protein Segments in the LIM Domain Protein RIL Mol. Biol. Cell, March 1, 1998; 9(3): 671 - 683. [Abstract] [Full Text] |
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J. J. Breen, A. D. Agulnick, H. Westphal, and I. B. Dawid Interactions between LIM Domains and the LIM Domain-binding Protein Ldb1 J. Biol. Chem., February 20, 1998; 273(8): 4712 - 4717. [Abstract] [Full Text] [PDF] |
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L. W. Jurata, S. L. Pfaff, and G. N. Gill The Nuclear LIM Domain Interactor NLI Mediates Homo- and Heterodimerization of LIM Domain Transcription Factors J. Biol. Chem., February 6, 1998; 273(6): 3152 - 3157. [Abstract] [Full Text] [PDF] |
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D. O'Keefe, S Thor, and J. Thomas Function and specificity of LIM domains in Drosophila nervous system and wing development Development, January 10, 1998; 125(19): 3915 - 3923. [Abstract] [PDF] |
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M Grigoriou, A. Tucker, P. Sharpe, and V Pachnis Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development Development, January 6, 1998; 125(11): 2063 - 2074. [Abstract] [PDF] |
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H. A. Louis, J. D. Pino, K. L. Schmeichel, P. Pomies, and M. C. Beckerle Comparison of Three Members of the Cysteine-rich Protein Family Reveals Functional Conservation and Divergent Patterns of Gene Expression J. Biol. Chem., October 24, 1997; 272(43): 27484 - 27491. [Abstract] [Full Text] [PDF] |
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P. Pomies, H. A. Louis, and M. C. Beckerle CRP1, a LIM Domain Protein Implicated in Muscle Differentiation, Interacts with alpha -Actinin J. Cell Biol., October 6, 1997; 139(1): 157 - 168. [Abstract] [Full Text] [PDF] |
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D. J. Roof, A. Hayes, M. Adamian, A. H. Chishti, and T. Li Molecular Characterization of abLIM, a Novel Actin-binding and Double Zinc Finger Protein J. Cell Biol., August 11, 1997; 138(3): 575 - 588. [Abstract] [Full Text] [PDF] |
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R. Konrat, R. Weiskirchen, B. Krautler, and K. Bister Solution Structure of the Carboxyl-terminal LIM Domain from Quail Cysteine-rich Protein CRP2 J. Biol. Chem., May 2, 1997; 272(18): 12001 - 12007. [Abstract] [Full Text] [PDF] |
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