Disease relevance of PDLIM5

• ENH is up-regulated during neural differentiation, and its ectopic expression in neuroblastoma cells leads to translocation of Id2 from the nucleus to the cytoplasm, with consequent inactivation of transcriptional and cell-cycle-promoting functions of Id2 [1].
• Finally, the differentiated neural crest-derived tumor ganglioneuroblastoma coexpresses Id2 and ENH in the cytoplasm of ganglionic cells [1].
• Nail patella syndrome (NPS) is caused by mutations in LMX1B, encoding a LIM homeodomain transcription factor [2].
• Chimeric transcripts were isolated from two lipomas in which HMGI-C DNA-binding domains (AT hook motifs) are fused to either a LIM or an acidic transactivation domain [3].
• The LIM domain protein rbtn2 is associated with T cell acute leukemias [4].

Psychiatry related information on PDLIM5

• Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia [5].
• They also suggest that ENH is a restraining factor of the oncogenic activity of Id proteins in neural tumors [1].
• Recently, the LIM mRNA expression in postmortem brains and immortalized lymphoblastoid cells from mood disorder patients was reported to be changed and seems to be involved in its pathophysiology [6].

High impact information on PDLIM5

• These oncogenes (Ttg1, Ttg2, SCL, LylI, H0X11) all belong to classic families of transcription factors, possessing LIM domains, helix-loop-helix motifs, or homeodomains [7].
• A two-hybrid screen identified the LIM protein Ajuba as an Aurora-A binding protein [8].
• We show here that migfilin, a LIM-containing protein, localizes to cell-matrix adhesions, associates with actin filaments, and is essential for cell shape modulation [9].
• The core secondary structures are similar to a rabphilin-3A Zn2+-binding domain and to the C1 and LIM domains [10].
• To define the molecular events involved in this process, we have analyzed the function of WNT7a, a secreted factor expressed in the dorsal ectoderm, and LMX1, a LIM homeodomain transcription factor expressed in the dorsal mesenchyme [11].

Chemical compound and disease context of PDLIM5

• Conversely, silencing of ENH by RNA interference prevents cytoplasmic relocation of Id2 in neuroblastoma cells differentiated with retinoic acid [1].
• Here we describe the use of commercially available precast 2-DE gels for performing nonreducing/non-urea 2-DE of proteins extracted from the human colon cancer cell line LIM 1215 with 0.3% Triton X-100 that permit the identification of antigens with conformational determinants by immunoblot analysis [12].
• We report that, when 5-FU at 0.125 and 0.25 micrograms/ml was combined with SMS 201.995 at 10(-12) x 2 to 10(-8) x 2M, an enhanced inhibition of in-vitro growth of two human colorectal cancer cell lines (C170 and LIM 1215) was achieved [13].

Biological context of PDLIM5

• A novel human gene cDNA was successfully cloned from the human fetal brain cDNA library constructed by our lab, and this gene was termed PDLIM5 after acquiring the agreement of HUGO [14].
• CONCLUSIONS: These results suggest that PDLIM5 might play a role in genetic susceptibility to schizophrenia [15].
• Due to very restricted knowledge on cytoskeletal changes in trophoblast, we analyzed the protein expression of an actin stress fiber-associated protein, the carboxy-terminal LIM domain protein (CLP36) [16].
• LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and the N-type calcium channel alpha-1B subunit and modulates neuronal calcium signaling [6].
• The LIM domain comprising two zinc-finger motifs is found in a variety of proteins and has been proposed to direct protein-protein interactions [17].

Anatomical context of PDLIM5

• RT-PCR experiment revealed that the expression level of PDLIM5 in brain, skeletal muscle, prostate, colon and leukocyte is obviously higher than that in other tissues [14].
• Expression of PDLIM5 was quantified by real-time quantitative polymerase chain reaction (PCR) in postmortem prefrontal cortex of 34 schizophrenia patients [15].
• Upon treatment of the cells with phorbol ester, ENH in the membrane fraction was translocated to the cytosol fraction in vivo [17].
• Clik1: a novel kinase targeted to actin stress fibers by the CLP-36 PDZ-LIM protein [18].
• We have previously reported the altered expressions of HSPF1 and LIM in the lymphoblastoid cell lines (LCLs) derived from Japanese patients with bipolar disorder (bipolar I disorder) [19].

Associations of PDLIM5 with chemical compounds

• Deletion analysis demonstrated that any single LIM domain of ENH associates with the NH2-terminal region of PKC [17].
• Other regulatory mechanisms in animal cells include binding of phosphoinositides, phosphorylation by LIM kinases on a single serine, and changes in pH [20].
• The protein encoded by lmx-1 also contains two amino-terminal cysteine/histidine-rich "LIM" domains [21].
• PINCH, which contains an array of five LIM domains, has been implicated as a platform for multiple protein-protein interactions that mediate integrin signaling within focal adhesions [22].
• Conserved cysteine and histidine residues in the LIM domains suggest a metal-binding role [23].

Other interactions of PDLIM5

• In addition, we found the altered expression of LIM and HSPF1 both in the brains and lymphoblastoid cells in bipolar disorder [24].
• From gene expression analysis, PDLIM5, somatostatin, and the mtDNA 3243 mutation were found to be related to bipolar disorder [25].

Analytical, diagnostic and therapeutic context of PDLIM5

• Western blot studies of muscle tissues using a non-isoform-specific anti-ENH antibody revealed that ENH4 is present only in skeletal muscle and that there is a specific distribution of ENH members between skeletal and cardiac muscles, which is different in human and mouse [26].
• BACKGROUND: Results of recent DNA microarray analyses of postmortem brains of patients with schizophrenia revealed that expression of the PDZ and LIM domain 5 gene (PDLIM5) is increased [15].
• Northern blot analysis revealed that 1.9 kb of the hENH messenger RNA was predominantly expressed in heart and skeletal muscle, while 5.6 kb of the hENH messenger RNA was ubiquitously expressed in various human tissues [27].
• An emerging theme is that LIM proteins might function as biosensors that mediate communication between the cytosolic and the nuclear compartments [28].
• Transfection analyses of sequential carboxyl-terminal truncations of the four individual LIM motifs and site-directed mutagenesis of LIM domains 1, 2, and 3, as well as deletion mutagenesis, revealed that the principal mechanism of targeting paxillin to focal adhesions is through LIM3 [29].

References