Disease relevance of FHL1

• In parallel studies the effects of FHL1 and PNL on plated melanoma cells from cell lines and short-term cultures were compared [1].
• FHL1 was significantly underexpressed in carcinomas compared to adenomas in the independent panel of tumors [2].
• Conversely, SLIM1 mRNA levels decrease during muscle atrophy [3].
• FHL1B is probably related to neural differentiation and certain fragile X syndrome [4].
• Elevated SLIM1 mRNA expression has been associated with postnatal skeletal muscle growth and stretch-induced muscle hypertrophy in mice [3].

High impact information on FHL1

• To increase our ability to detect clonality, we developed simple TCA for detecting the transcripts of 2 additional X-chromosome genes: Bruton tyrosine kinase (BTK) and 4-and-a-half LIM domain 1 (FHL1) [5].
• Immunofluorescence studies with cells expressing full-length FHL proteins or their deletion mutants showed that FHL2 and FHL3 but not FHL1 colocalize with integrins at cell adhesion sites [6].
• Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1. Localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication [7].
• SLIM1 contains an N-terminal single zinc finger followed by four LIM domains [7].
• SLIM1 localized to the cytosol of Sol8 myoblasts and myotubes [7].

Biological context of FHL1

• We have amplified and sequenced a novel, alternatively spliced variant of a human gene coding for the four-and-a-half LIM domain protein 1 (FHL1) [4].
• The FHL1 gene was located to human chromosome at Xq27.2 by somatic cell hybrid mapping, fluorescent in situ hybridization (FISH) and radiation hybrid mapping [8].
• FHL1 is unique when compared with other LIM-only proteins because it possesses an odd number of zinc fingers [8].
• Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1) [8].
• This gene is located at chromosome Xq27 and the spliced variant is named FHL1B [4].

Anatomical context of FHL1

• RT-PCR results revealed that the expression of FHL1 is not restricted in skeletal muscle and heart, but is widely distributed in other tissues, including brain, placenta, lung, liver, kidney and pancreas, albeit as a low abundance transcript [4].
• Collectively, these results suggest distinct roles for SLIM1 and SLIMMER in focal adhesions and nuclear-cytoplasmic communication [7].
• Recombinant green fluorescent protein-SLIM1 localized to the cytoplasm and associated with focal adhesions and actin filaments in COS-7 cells, while green fluorescent protein-SLIMMER was predominantly nuclear [7].
• Skeletal muscle LIM protein 1 (SLIM1/FHL1) induces alpha 5 beta 1-integrin-dependent myocyte elongation [3].
• SLIM1 mRNA was also demonstrated in the hindbrain, neural tube and somites [9].

Associations of FHL1 with chemical compounds

• We show that FHL-1 presents a higher binding affinity for S. pyogenes than factor H because it carries a hydrophobic, high-affinity, GAS binding site in addition to the heparin binding site in SCR7 [10].
• Since the 25-HC, 9-cis RA and 15d-PGJ2 were ligands for the LXR, RXRalpha and PPARgamma respectively, there might be a functional positive cross-talk between LXR and RXRalpha pathways and a negative cross-talk between PPARgamma and LXR and/or RXRalpha pathways in the regulation of SLIM1 expression [11].
• In addition, an over-production of SLIM1 in the cells resulted in a change in the cell-shape into a spindle-like form, which is identical to that observed after a prolonged treatment of the cells with cholesterol [11].
• Up-regulation of skeletal muscle LIM protein 1 gene by 25-hydroxycholesterol may mediate morphological changes of rat aortic smooth muscle cells [11].
• OBJECTIVE: To evaluate ease of insertion, acceptability and endometrial safety of a novel, miniature intrauterine, T-shaped, levonorgestrel (LNG)-releasing intrauterine system (IUS), Femilis Slim LNG-IUS (Contrel Research, Belgium), combined with parenteral estrogen substitution therapy (EST) in postmenopausal women [12].

Other interactions of FHL1

• Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of a human LIM-only protein (FHL1) [13].
• Expressions of all three genes (SLIM1, SM alpha-actin and CNN-1) were simultaneously elevated in the cells treated with 9-cis retinoic acid (RA) [11].
• Quantitative PCR was employed to validate expression levels for caldesmon, SWI/SNF (BAF60b), and four-and-a-half LIM domains 1 [14].

Analytical, diagnostic and therapeutic context of FHL1

• The interaction between FHL1 and myosin-binding protein C was confirmed using co-immunoprecipitation of recombinant and endogenous proteins [15].
• Northern blot analysis confirmed strikingly high expression of SLIM1 in skeletal muscle and heart, with much lower expression observed in several other tissues including colon, small intestine and prostate [16].
• The SLIM1 gene was assigned to human chromosome Xq26 using fluorescence in situ hybridization [16].
• Western blot analysis showed an initial decrease followed by an increase in SLIM1 expression during differentiation [3].
• The seroprevalence of Orientia tsutsugamushi, Rickettsia typhi, and TT118 spotted fever group (SFG) rickettsiae in 300 rubber estate workers in Slim River, Malaysia was determined in December 1996 and March 1997 [17].

References