Disease relevance of Fhl1

• When expressed in F9 embryonal carcinoma cells, KyoT1 and KyoT2 were localized in the cytoplasm and the nucleus, respectively [1].
• Taken together, these data indicate the potential importance of this FHL family in the development and maintenance of the cardiovascular system and striated muscle, and suggest that FHL1 may play a role in the development of heart disease [2].
• It has been demonstrated that Borrelia hermsii, a causative agent of relapsing fever, produces a factor H (FH) and FH-like protein 1 (FHL-1) binding protein [3].
• BetaAR blockade treatment reversed the cardiomyopathy and suppressed the increased expression of UCP2 and FHL1 in mice overexpressing Gsalpha [4].

High impact information on Fhl1

• Thus, Rho signaling exerts an unexpectedly complex role in keratinocyte differentiation, which is coupled with induction of KyoT1/2, a LIM domain protein gene with a potentially important role in control of cell self renewal [5].
• Strong expression of KyoT mRNAs was detected in skeletal muscle and lung, with a predominance of KyoT1 mRNA [1].
• Collectively, these analyses indicate that FH/FHL-1 binding is a widespread virulence mechanism for B. hermsii and provide insight into the genetic and antigenic structure of FhbA [3].
• Disruption of the actin cytoskeleton by cytochalasin D did not inhibit nuclear localization of SLIM1 in integrin-activated cells [6].
• Overexpression of SLIM1 in Sol8 myoblasts inhibited cell adhesion and promoted cell spreading and migration [6].

Biological context of Fhl1

• Four and a half LIM domain protein 1 (FHL1) was initially described as an abundant skeletal muscle protein with four LIM domains and a GATA like zinc finger [7].
• FHL1 and FHL3 mRNAs were reciprocally expressed in the murine C2C12 skeletal muscle cell line and this suggested that the pattern of expression was linked to key events in myogenesis [8].
• Differential expression was observed in genes from 22 Gene Ontology Slim categories, including those associated with ion transport and calcium ion binding [9].

Anatomical context of Fhl1

• Green fluorescent protein-tagged SLIM1 shuttled in the nucleus of untransfected NIH 3T3 cells, in a heterokaryon fusion assay [6].
• These studies show SLIM1 localizes in an integrin-dependent manner to the nucleus and focal adhesions where it functions downstream of integrin activation to promote cell spreading and migration [6].
• However, after inhibition of integrin signaling either by plating on poly-l-lysine or by soluble RGD peptide, SLIM1 localized diffusely in the cytosol, with decreased nuclear expression [6].
• In contrast, FHL1C is specifically expressed in testis, skeletal muscle, and heart at a relatively low level compared with FHL1 [10].

Associations of Fhl1 with chemical compounds

• Skeletal muscle LIM protein 1 regulates integrin-mediated myoblast adhesion, spreading, and migration [6].
• Following depletion, seven rats were randomly assigned to each of five repletion diets containing folic acid, Complan, Slim Fast, Opti-Fuel2 or Cola Coa calculated to provide 200 microg folate/kg of each diet [11].

Other interactions of Fhl1

• Here, we describe the cloning and expression patterns of three members of the four and a half LIM domain-only protein family, FHL1, 2, and 3, from mouse [2].
• Six genes were up-regulated in comparison to those in unfractured bones and these included three genes previously identified but never shown to be present in fractures, periostin, calumenin, and FHL-1 [12].

Analytical, diagnostic and therapeutic context of Fhl1

• Sequence analysis indicated that FHL1C is the human homolog of murine KyoT2 [10].
• The interaction between FHL1 and myosin-binding protein C was confirmed using co-immunoprecipitation of recombinant and endogenous proteins [13].
• The Northern blot and RT-PCR results revealed that FHL1 is widely expressed in human tissues, including skeletal muscle and heart at a high level, albeit as a relatively low abundance transcript in brain, placenta, lung, liver, kidney, pancreas, and testis [10].
• Western blot analysis using specific affinity-purified anti-SLIM1 antipeptide antibodies demonstrated a 32 kDa polypeptide in the aorta and atria of rabbit heart, but not in vena cava, interventricular septum or ventricular muscle [14].

References