Common metal ion coordination in LIM domain proteins

Kosa, Jessica L.; Michelsen, James W.; Louis, Heather A.; Olsen, Jay I.; Davis, Darrell R.; Beckerle, Mary C.; Winge, Dennis R.

doi:10.1021/bi00168a011

Cited by 82 publications

(57 citation statements)

References 43 publications

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“…4B). These mutant LIM domains are not expected to bind any zinc atom or to fold correctly (35,46). Yeast cells with any one of these mutant forms of Dbm1p as their only source of Dbm1p bud predominantly in a bipolar fashion, just like cells that totally lack Dbm1p (Table 6), thus indicating that both of the LIM domains of Dbm1p are required for its normal function.…”

Section: Which Gtpase Is Regulated By Dbm1p In Vivo?mentioning

confidence: 99%

The LIM Domain-Containing Dbm1 GTPase-Activating Protein Is Required for Normal Cellular Morphogenesis in Saccharomyces cerevisiae

Chen

Chan

1996

Molecular and Cellular Biology

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Normal cell growth in the yeast Saccharomyces cerevisiae involves the selection of genetically determined bud sites where most growth is localized. Previous studies have shown that BEM2, which encodes a GTPaseactivating protein (GAP) that is specific for the Rho-type GTPase Rho1p in vitro, is required for proper bud site selection and bud emergence. We show here that DBM1, which encodes another putative Rho-type GAP with two tandemly arranged cysteine-rich LIM domains, also is needed for proper bud site selection, as haploid cells lacking Dbm1p bud predominantly in a bipolar, rather than the normal axial, manner. Furthermore, yeast cells lacking both Bem2p and Dbm1p are inviable. The nonaxial budding defect of dbm1 mutants can be rescued partially by overproduction of Bem3p and is exacerbated by its absence. Since Bem3p has previously been shown to function as a GAP for Cdc42p, and also less efficiently for Rho1p, our results suggest that Dbm1p, like Bem2p and Bem3p, may function in vivo as a GAP for Cdc42p and/or Rho1p. Both LIM domains of Dbm1p are essential for its normal function. Point mutations that alter single conserved cysteine residues within either LIM domain result in mutant forms of Dbm1p that can no longer function in bud site selection but instead are capable of rescuing the inviability of bem2 mutants at 35؇C.

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Section: Which Gtpase Is Regulated By Dbm1p In Vivo?mentioning

confidence: 99%

The LIM Domain-Containing Dbm1 GTPase-Activating Protein Is Required for Normal Cellular Morphogenesis in Saccharomyces cerevisiae

Chen

Chan

1996

Molecular and Cellular Biology

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“…X~-C-X~-H-(C)-X~-C) which is also present as a two-copy tandem in 'Zn-finger' proteins (Wang et al 1992;Levenson et al 1993;Kosa et al 1994).…”

Section: And Contains a Metal-binding Lim Motif (C-x~-c-xi~-i~-h-x~-c-x~mentioning

confidence: 99%

Copper and zinc metabolism in health and disease: speciation and interactions

Bremner¹,

Beattie²

1995

Proc. Nutr. Soc.

135

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It has long been evident that the metabolism of trace elements cannot be considered in isolation. A wide range of nutritional and physiological factors can influence their uptake, transport and storage, with subsequent enhancement of susceptibility to deficiency or toxicity states. Interactions occur with other trace elements and these can be classified as competitive or non-competitive, direct or indirect. However, their physiological or toxicological significance is sometimes debatable, partly because they were demonstrated under extreme experimental conditions where massive doses of the antagonistic metal were administered, often by parenteral routes and to animals whose trace element status was already severely compromised. Our understanding of the mechanisms of the interactions is frequently limited and indeed in only a few cases has it been possible to describe these on a molecular basis.It is almost traditional to cite the early work of Hill & Matrone (1970) as the first serious attempt to describe trace element interactions on a rational basis. They postulated that elements with similar physical or chemical properties will act antagonistically to each other biologically. The implication was that such metals could compete for binding sites on transport proteins or on enzymes requiring metals as co-factors. Over subsequent years, much evidence was produced in support of this view but rarely was the specific site of interaction identified, other than at tissue level. In part this reflected somewhat embarrassing limitations in our knowledge of the proteins involved in the intracellular and extracellular transport and storage of trace metals. 1988). This casts some doubt on the mutuality of the interaction. Most of the early investigations were largely descriptive and they did little to elucidate the precise molecular basis or locus of the interaction.Cu and Zn occupy a similar part of the periodic table, the Zn2+ and Cuf ions being isoelectronic and having similar ionic radii. Both metals readily form chelates with 0-, S-, or N-containing ligands but not always with the same stereochemical arrangement of bonds. However, unlike Zn which occurs in only one valency state, Cu can occur in two, as Cu+ and Cu2+; indeed there have been suggestions that Cu3+ may also have a https://www.cambridge.org/core/terms. https://doi

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“…One intact LIM domain contains two zinc fingers which mediate protein-protein interactions. 2,3 Due to the presence of four and a half LIM domains, members of the FHL subfamily are able to interact with a broad variety of proteins. There are five members described so far, FHL1-FHL4 and ACT (activator of CREM in testis).…”

Section: Introductionmentioning

confidence: 99%

FHL2 Regulates Cell Cycle-Dependent and Doxorubicin-Induced p21Cip1/Waf1 Expression in Breast Cancer Cells

Martin¹,

Kleiber²,

Wixler³

et al. 2007

Cell Cycle

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© 2 0 0 7 L A N D E S B I O S C I E N C E . D O N O T D I S T R I B U T E .[Cell Cycle 6:14, 1779-1788, 15 ABSTRAcTThe transcriptional cofactor FHL2 interacts with a broad variety of transcription factors and its expression is often deregulated in various types of cancer. Here we analyzed for the first time the molecular function of FHL2 in breast cancer. FHL2 is overexpressed in almost all human mammary carcinoma samples tested but not in normal breast tissues and only low levels of FHL2 expression were present in four premalignant ductal carcinoma in situ (DCIS). Cell cycle analysis revealed an upregulation of endogenous FHL2 towards G 2 /M in MDA-MB 231 cells and an accelerated G 2 /M transition when FHL2 expression was suppressed in these cells. In search for G 2 /M specific target genes regulated by FHL2, we found that expression of the cell cycle inhibitor p21 Cip1/Waf1 (hereafter p21) is dependent on FHL2 in MDA-MB 231 breast cancer cells. Downregulation of FHL2 by shRNA abrogated the cell cycle dependent upregulation of p21 as well as the induction of p21 in response to treatment with the DNA damaging agent doxorubicin. FHL2-dependent p21 expression occurs in a p53-independent manner and p21 expression can be downregulated by specific inhibition of mitogen-activated protein kinases (MAPKs), implicating an involvement of MAPK signaling in this regulation. Analysis of FHL2 contribution to the MAPK signaling identified FHL2 as an important downstream effector of MAPKs in breast cancer cells, capable of transactivating endogenous AP1 target genes as well as AP1 dependent reporter genes. Finally, downregulation of FHL2 reduces the ability of MDA-MB 231 cells to form colonies in soft agar, while FHL2 overexpression enhances colony formation of breast cancer cells. Thus, our findings indicate that overexpression of the transcriptional cofactor FHL2 contributes to breast cancer development by mediating transcriptional activation of MAPK target genes known to be involved in cancer progression, such as p21.

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Common metal ion coordination in LIM domain proteins

Cited by 82 publications

References 43 publications

The LIM Domain-Containing Dbm1 GTPase-Activating Protein Is Required for Normal Cellular Morphogenesis in Saccharomyces cerevisiae

The LIM Domain-Containing Dbm1 GTPase-Activating Protein Is Required for Normal Cellular Morphogenesis in Saccharomyces cerevisiae

Copper and zinc metabolism in health and disease: speciation and interactions

FHL2 Regulates Cell Cycle-Dependent and Doxorubicin-Induced p21Cip1/Waf1 Expression in Breast Cancer Cells

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