Analysis of the adaptor function of the LIM domain‐containing protein FHL2 using an affinity chromatography approach

Mourabit, Haquima El; Müller, Stefan; Tunggal, Lucy; Paulsson, Mats; Aumailley, Monique

doi:10.1002/jcb.20096

Cited by 12 publications

(12 citation statements)

References 38 publications

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“…Twentytwo proteins were retained when cytosolic fractions of human fibroblast Wi26 cells were separated over a column to which FHL2 was coupled. These proteins included metabolic enzymes, chaperones, signalling pathway components, and molecules involved in ubiquitination and in the organisation and dynamics of the cytoskeleton [80]. The identification of these proteins suggests that FHL2 may be involved in the nucleation of nascent cell adhesion structures by bringing key effector proteins in close proximity and in the control of actin bundling [80].…”

Section: Fhl2 and Signalling Transductionmentioning

confidence: 99%

“…These proteins included metabolic enzymes, chaperones, signalling pathway components, and molecules involved in ubiquitination and in the organisation and dynamics of the cytoskeleton [80]. The identification of these proteins suggests that FHL2 may be involved in the nucleation of nascent cell adhesion structures by bringing key effector proteins in close proximity and in the control of actin bundling [80]. Moreover, the presence of FHL2 in different subcellular localizations and the physical association of FHL2 with proteins such as receptors, receptor-linked proteins, signal transmitter proteins and transcription factors (table 2) further support a role for FHL2 as a signal transducer [34,43].…”

Section: Fhl2 and Signalling Transductionmentioning

confidence: 99%

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The multifunctional roles of the four-and-a-half-LIM only protein FHL2

Johannessen

Møller

Hansen

et al. 2006

Cell. Mol. Life Sci.

214

256

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Numerous cellular processes require the concerted action of multiple proteins that assemble in functional complexes. Protein-protein interaction domains allow specific proteins to combine with certain partners. Specificity of protein-protein association can be obtained by an interaction code predicted by conserved amino acid sequences. One of the protein-protein interaction motifs is the LIM domain, a conserved cysteine-rich module present in more than 100 different human proteins. The human four-and-a-half-LIM-only protein family consists of the members FHL1, FHL2, FHL3, FHL4 and ACT. They are expressed in a cell- and tissue-specific manner and participate in various cellular processes, including regulation of cell survival, transcription and signal transduction. Here, we review the current knowledge of the best-studied member of this family, FHL2. We describe the transcription regulation, the expression profile, the interaction partners, the subcellular localization, the biological functions and discuss the possible involvement of FHL2 in human diseases.

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Section: Fhl2 and Signalling Transductionmentioning

confidence: 99%

Section: Fhl2 and Signalling Transductionmentioning

confidence: 99%

The multifunctional roles of the four-and-a-half-LIM only protein FHL2

Johannessen

Møller

Hansen

et al. 2006

Cell. Mol. Life Sci.

214

256

View full text Add to dashboard Cite

show abstract

“…The acronym LIM derives from Lin-11, I sl-1, and Mec-3, three transcription factors in which a specific motif, LIM, was originally described [18,33]. LIM domains are characterized by the cysteine-rich consensus CX2CX 16−23 HX 2 CX 2 CX 2 CX 16−21 CX 2−3 (C/H/D) [34], and function as adapters and modifiers in protein interactions [35].…”

Section: Fhl2: a Ski Enigmatic Partnermentioning

confidence: 99%

SKI pathways inducing progression of human melanoma

Reed

Lin

Chen

et al. 2005

Cancer Metastasis Rev

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The proteins SKI and SnoN are implicated in processes as diverse as differentiation, transformation and tumor progression. Until recently, SKI was solely viewed as a nuclear protein with a principal function of inhibiting TGF-beta signaling through its association with the Smad proteins. However, new studies suggest that SKI plays additional roles not only inside but also outside the nucleus. In normal melanocytes and primary non-invasive melanomas, SKI localizes predominantly in the nucleus, whereas in primary invasive melanomas SKI displays both nuclear and cytoplasmic localization. Intriguingly, metastatic melanoma tumors display nuclear and cytoplasmic or predominantly cytoplasmic SKI distribution. Cytoplasmic SKI is functional, as it associates with Smad3 and prevents its nuclear localization mediated by TGF-beta. SKI can also function as a transcriptional activator, targeting the beta -catenin pathway and activating MITF and NrCAM, two proteins involved in survival, migration and invasion. Intriguingly, SKI appears to live a dual life, one as a tumor suppressor and another as a transforming protein. Loss of one copy of mouse ski increases susceptibility to tumorigenesis in mice, whereas its overexpression is associated with cancer progression of human melanoma, esophageal, breast and colon. The molecular reasons for such dramatic change in SKI function appear to result from new acquired activities. In this review, we discuss the mechanisms by which SKI regulates crucial pathways involved in the progression of human malignant melanoma.

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“…LIM proteins mediate protein-protein interactions and sometimes bind DNA or mediate nuclear localization (10,11). Multiple functions have been ascribed to FHL2, likely a result of its interaction with over 50 different proteins that are involved in most major signaling pathways (8).…”

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confidence: 99%

LIM-Only Protein FHL2 Is a Positive Regulator of Liver X Receptors in Smooth Muscle Cells Involved in Lipid Homeostasis

Kurakula

Sommer

Sokolović

et al. 2015

Molecular and Cellular Biology

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bThe LIM-only protein FHL2 is expressed in smooth muscle cells (SMCs) and inhibits SMC-rich-lesion formation. To further elucidate the role of FHL2 in SMCs, we compared the transcriptomes of SMCs derived from wild-type (WT) and FHL2 knockout (KO) mice. This revealed that in addition to the previously recognized involvement of FHL2 in SMC proliferation, the cholesterol synthesis and liver X receptor (LXR) pathways are altered in the absence of FHL2. Using coimmunoprecipitation experiments, we found that FHL2 interacts with the two LXR isoforms, LXR␣ and LXR␤. Furthermore, FHL2 strongly enhances transcriptional activity of LXR element (LXRE)-containing reporter constructs. Chromatin immunoprecipitation (ChIP) experiments on the ABCG1 promoter revealed that FHL2 enhances the association of LXR␤ with DNA. In line with these observations, we observed reduced basal transcriptional LXR activity in FHL2-KO SMCs compared to WT SMCs. This was also reflected in reduced expression of LXR target genes in intact aorta and aortic SMCs of FHL2-KO mice. Functionally, the absence of FHL2 resulted in attenuated cholesterol efflux to both ApoA-1 and high-density lipoprotein (HDL), in agreement with reduced LXR signaling. Collectively, our findings demonstrate that FHL2 is a transcriptional coactivator of LXRs and points toward FHL2 being an important determinant of cholesterol metabolism in SMCs.

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Analysis of the adaptor function of the LIM domain‐containing protein FHL2 using an affinity chromatography approach

Cited by 12 publications

References 38 publications

The multifunctional roles of the four-and-a-half-LIM only protein FHL2

The multifunctional roles of the four-and-a-half-LIM only protein FHL2

SKI pathways inducing progression of human melanoma

LIM-Only Protein FHL2 Is a Positive Regulator of Liver X Receptors in Smooth Muscle Cells Involved in Lipid Homeostasis

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