“…Therefore, the dysregulation of LMO4 has been implicated in the carcinogenesis and metastasis of a variety of human cancers. Studies have indicated that LMO4 overexpression may disrupt the normal tumor suppressor activities of Tip, promoting breast cancer progression (2), and affecting lung cancer patient survival (3). A number of studies have found LMO4 highly expressed at sites of active epithelial-mesenchymal interactions, and LMO4 can interact with signaling pathways involved in epithelial-mesenchymal signaling (4), leading to an increase in stromal cell invasion and migration.…”
Background: The aims of this study were to analyze the association of LMO4 with non-small-cell lung cancer (NSCLC) survival rate, and to determine its functional role and signaling pathway in lung cancer. Methods: Immunohistochemistry (IHC) was used to detect the expression of LMO4 in NSCLC cell lines and tumor tissues. Migration and invasion ability was detected respectively by wound healing test and transwell test. Immunofluorescence and western blot were detected of AKT/PI3K pathway related genes MAPK, PI3K, AKT. Results: LMO4 has high expression level of NSCLC cell lines and tumor tissues, and correlated with a lower survival rate. LMO4 can regulate the migration and invasion of NSCLC cells through the AKT/PI3K pathway. Conclusions: LMO4 could serve as a promising biomarker and therapeutic target for NSCLC.
“…Therefore, the dysregulation of LMO4 has been implicated in the carcinogenesis and metastasis of a variety of human cancers. Studies have indicated that LMO4 overexpression may disrupt the normal tumor suppressor activities of Tip, promoting breast cancer progression (2), and affecting lung cancer patient survival (3). A number of studies have found LMO4 highly expressed at sites of active epithelial-mesenchymal interactions, and LMO4 can interact with signaling pathways involved in epithelial-mesenchymal signaling (4), leading to an increase in stromal cell invasion and migration.…”
Background: The aims of this study were to analyze the association of LMO4 with non-small-cell lung cancer (NSCLC) survival rate, and to determine its functional role and signaling pathway in lung cancer. Methods: Immunohistochemistry (IHC) was used to detect the expression of LMO4 in NSCLC cell lines and tumor tissues. Migration and invasion ability was detected respectively by wound healing test and transwell test. Immunofluorescence and western blot were detected of AKT/PI3K pathway related genes MAPK, PI3K, AKT. Results: LMO4 has high expression level of NSCLC cell lines and tumor tissues, and correlated with a lower survival rate. LMO4 can regulate the migration and invasion of NSCLC cells through the AKT/PI3K pathway. Conclusions: LMO4 could serve as a promising biomarker and therapeutic target for NSCLC.
“…5A). In terms of the LIDs from LIM-7 and ISL1, the sequence identity is low, and it is not easy to confidently predict binding registers for LIM-LID interactions 43, 44 . However, the SWISS-MODEL prediction was identical to our manual alignment (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Another characteristic feature of LIM-LID interactions 26 that is conserved in this model is the burial of the LIM-7 V353 and LIM-7 I368 sidechains in between the two zinc-binding modules in each LIM domain of CEH-14. Note that although these features are structurally conserved, mutation of these buried residues can have surprisingly little effect, possibly due to plasticity in the hydrophobic pockets 31, 44 .Figure 5Conserved and unusual features of LHX3-Islet family LIM-HD interactions in C. elegans proteins. ( A ) Overlay of the LHX3 LIM1+2 (black ribbon/transparent grey surface representation)–ISL1 LID (cyan) crystal structure (1RGT Chain B) and a simple homology model of CEH-14(orange)–LIM-7(purple).…”
LIM-Homeodomain (LIM-HD) transcription factors are highly conserved in animals where they are thought to act in a transcriptional ‘LIM code’ that specifies cell types, particularly in the central nervous system. In chick and mammals the interaction between two LIM-HD proteins, LHX3 and Islet1 (ISL1), is essential for the development of motor neurons. Using yeast two-hybrid analysis we showed that the Caenorhabditis elegans orthologs of LHX3 and ISL1, CEH-14 and LIM-7 can physically interact. Structural characterisation of a complex comprising the LIM domains from CEH-14 and a LIM-interaction domain from LIM-7 showed that these nematode proteins assemble to form a structure that closely resembles that of their vertebrate counterparts. However, mutagenic analysis across the interface indicates some differences in the mechanisms of binding. We also demonstrate, using fluorescent reporter constructs, that the two C. elegans proteins are co-expressed in a small subset of neurons. These data show that the propensity for LHX3 and Islet proteins to interact is conserved from C. elegans to mammals, raising the possibility that orthologous cell specific LIM-HD-containing transcription factor complexes play similar roles in the development of neuronal cells across diverse species.
“…However, tethered complexes are not amenable to standard quantitative binding studies. Yeast‐two hybrid (Y2 H) assays suggest that the interactions of LMO4 with CtIP and Deaf1 are significantly weaker than with LDB1 ,. Homologous competition ELISA experiments using complexes in which the tether has been cut by a protease yielded estimates of LDB1 LID :LMO2/4 LIM1+2 affinity ( K d =20 and 10 n m respectively), but are not suited to weaker interactions due to multiple washing steps.…”
Section: Figurementioning
confidence: 99%
“…FRET‐dilution assays in which concentrated samples of cut complexes were serially diluted gave affinity estimates of K d =1.4±0.3 n m and 31±3 n m for LMO4 LIM1+2 binding to LDB1 LID (WT) and the I322A mutant, respectively (Figure A and Table S1), in good agreement with the competition experiments. Attempts were made to assess the weaker binding of CtIP LID to LMO4 LIM1+2 . We modified the dilution experiment by spiking in YFP‐CtIP LID to promote complex formation, with the resultant estimate of affinity measured as K d =9±2 μ m (Figure A).…”
We have developed Fçrster resonance energy transfer (FRET)-based experiments for measuring the binding affinity,o ff-rates,a nd inferred on-rates for interactions between af amily of transcriptional regulators and their intrinsically disordered binding partners.I tw as difficult to evaluate these interactions previously,a st he transcriptional regulators are obligate binding proteins that aggregate in the absence of ab inding partner.T he assays rely on fusion constructs where binding domains are linked by af lexible tether containing as pecific protease site,w ith fluorescent proteins at either end that displayF RET when the complex is formed. Loss of FRET is monitored after cutting the tether followed by dilution or competition with an on-fluorescent peptide.T hese methods allowed aw ide range of binding affinities (10 À9 -10 À5 m)t o be determined. Our data indicate that interactions of closely related proteins can have surprisingly different binding properties.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
