LIM domains: multiple roles as adapters and functional modifiers in protein interactions

Dawid, Igor B.; Breen, J. J.; Toyama, Reiko

doi:10.1016/s0168-9525(98)01424-3

Cited by 553 publications

(472 citation statements)

References 64 publications

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“…The LIM domain is a cysteine-and histidine-rich double zinc-finger motif named after the three-homeodomain proteins: Lin-l 1, Isl-1 and Mec-3 (Way and Chalfie, 1988;Freyd et al, 1990;Karlsson et al, 1990). This domain is present in a wide range of proteins whose functions include many fundamental biological processes such as cell lineage specification, cytoskeleton organization and organ development (Dawid et al, 1998;Bach, 2000;Kadrmas and Beckerle, 2004). In addition, some LIM domain-containing proteins are also involved in pathological processes such as oncogenesis (e.g.…”

Section: Introductionmentioning

confidence: 99%

ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

2006

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We have recently identified ZNF185 as a gene that is downregulated in prostate cancer (PCa), in part via epigenetic alteration, and maybe associated with disease progression. In this study, we cloned the ZNF185 cDNA from normal human prostate tissues and investigated its biological function. We show that ZNF185 is a novel actin-cytoskeleton-associated Lin-l 1, Isl-1 and Mec-3 (LIM) domain-containing protein that localizes to F-actin structures, and is enriched at focal adhesions. We find that the NH 2 -terminal region, which we designate the actintargeting domain, facilitates ZNF185 binding to actin in vitro and is both necessary and sufficient to mediate actin-cytoskeleton targeting of ZNF185, whereas the LIM domain, which is localized in the COOH-terminus is dispensable for this phenomenon. Interestingly, ectopic expression of full-length ZNF185, but not a mutant lacking the actin-targeting domain, could suppress proliferation and anchorage-independent growth of PCa cells. Together, our data suggest that ZNF185 may function as a tumor-suppressor protein by associating with the actincytoskeleton.

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Section: Introductionmentioning

confidence: 99%

ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

2006

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“…exons 2 -3) exhibited B90% homology with CRP2 and hsmlim genes . The deduced amino-acid sequence revealed that unlike CRP2 and hsmlim proteins (Dawid et al, 1995(Dawid et al, , 1998Weiskirchen et al, 1997), which expressed two LIM domains, the IL-10E1 protein consisted of a single LIM domain at the n-terminal region of the protein. Presumably, this difference between IL-10E1 and CRP2 or hsmlim might explain why IL-10E1 is overexpressed in prostate cancer cells and functions as an IL-10-responsive signal molecule.…”

Section: Discussionmentioning

confidence: 99%

“…The LIM domain consists of a 52 amino-acid sequence CX 2 CX 16 -23 HX 2 CX 2 CX 2 CX 16 -21 CX 2 -3 (C/H/D) motif, which typically has been associated with DNA-binding homeodomains and kinase domains (Freyd et al, 1990;Karlsson et al, 1990;Dawid et al, 1995Dawid et al, , 1998. The LIM domain has been recognised as a distinct protein motif within LIM homeodomain proteins by both genetic and biochemical methods (Freyd et al, 1990;Karlsson et al, 1990;Way and Chalfie, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…The LIM domain has been found to mediate 'protein -protein' interactions of cytoplasmic and nuclear proteins. NMR analysis of the solution structure of the c-terminal LIM domain of two of these proteins, CRP1 (Perez-Alvarado et al, 1994) and CRP2 (Konrat et al, 1997;Weiskirchen et al, 1997;Wadman et al, 1994), has shown that two zinc-fingers constitute a LIM domain, which represent two separated structural entities held together in a distinct configuration by hydrophobic interactions (Dawid et al, 1998). Moreover, the c-terminal LIM domain in CRP1 and CRP2 has been found to closely resemble the zinc-finger in the DNA-binding domain of GATA1, suggesting that the LIM domain might specifically bind DNA (Weiskirchen et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

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A novel IL-10 signalling mechanism regulates TIMP-1 expression in human prostate tumour cells

Wang

Stearns

2003

Br J Cancer

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We have previously reported that interleukin 10 (IL-10) signalling stimulated activation of a specific enhancer element, termed HTE-1, to promote tissue inhibitor of matrix metalloproteinase1 (TIMP-1) expression in human bone metastatic PC-3 subclone (PC-3 ML) cells. Recently, we have identified an IL-10 responsive signal molecule, termed IL-10E1, which binds the HTE-1 element and cloned the gene encoding for the 22 kDa protein. In this paper, we have examined the mechanism of IL-10/IL-10 receptor signalling in two distinct human prostate cell lines, a 'normal' prostate epithelial cell line, termed NPTX-1532 and highly metastatic PC-3 ML tumour cells. Signalling cascade studies revealed that IL-10 stimulated tyrosine phosphorylation of JAK1 and TYK2 receptor kinases and tyrosine phosphorylation of IL-10E1. Phosphorylation, triggered IL-10E1's rapid translocation to the nucleus by 10 -30 min. Deletion analysis combined with transient transfection experiments revealed that the n-terminal domain (B74 a.a.) of the IL-10E1 protein, the nt-nls peptide, was stimulated by IL-10 to translocate to the nucleus and induce TIMP-1 expression. Site-directed mutagenesis further showed that phosphorylation of two tyrosine moieties (Y57 and Y62) of the nt-nls peptide was required for IL-10 activation of signalling and TIMP-1 expression. The data demonstrate, for the first time, that IL-10 receptor signalling of TIMP-1 expression is regulated by tyrosine phosphorylation of a novel gene, IL-10E1, in human prostate cells.

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“…LIM domain proteins are known to be important in cell growth and differentiation, but have not previously been reported in osteoblasts. 58 In situ hybridization of developing limb buds from mouse embryos showed that LMP-1 transcripts appeared at the time and place of transition from hypertrophic cartilage to primary trabecular bone during endochondral ossification, and were also seen in areas of membranous bone formation.…”

Section: Introductionmentioning

confidence: 99%

Spine fusion by gene therapy

Yoon

Boden

2004

Gene Ther

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LIM domains: multiple roles as adapters and functional modifiers in protein interactions

Cited by 553 publications

References 64 publications

ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

A novel IL-10 signalling mechanism regulates TIMP-1 expression in human prostate tumour cells

Spine fusion by gene therapy

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