Disease relevance of LPP

• Using reverse transcriptase combined with polymerase chain reactions in the analysis of a number of lipoma cell lines and primary lipomas, it appeared that LPP is frequently rearranged also in cases without a cytogenetically detectable involvement of 3q27-q28 [1].
• A novel LPP fusion gene indicates the crucial role of truncated LPP proteins in lipomas and pulmonary chondroid hamartomas [2].
• In addition, a fusion of LPP to the mixed lineage leukemia (MLL) gene has been described in a case of acute myeloid leukemia [2].
• For example, HMGA2/LPP has been reported in lipoma, pulmonary chondroid hamartoma, and soft tissue chondroma [3].
• Pretreatment of macrophages with MCAF significantly enhanced their response to low concentrations of LPS, muramyl tripeptide, and a synthetic bacterial LPP, as measured by lysis of murine melanoma cells [4].

High impact information on LPP

• Here, we have identified the LIM domain protein LPP as a novel coregulatory binding partner for PEA3 [5].
• LPP can also functionally interact in a similar manner with the related family member ER81 [5].
• By manipulating LPP levels, we show that it acts to upregulate the transactivation capacity of PEA3 [5].
• Thus, we have uncovered a novel nuclear function for the LIM domain protein LPP as a transcriptional coactivator [5].
• As LPP continually shuttles between the cell periphery and the nucleus, it represents a potential novel link between cell surface events and changes in gene expression [5].

Biological context of LPP

• Here, we report the identification and characterization of the chromosome 3-derived translocation partner gene, which we have designated LPP (lipoma preferred partner gene) [1].
• RESULTS: To catch the role of LPP at sites of cell adhesion, we made an effort to identify binding partners of LPP [6].
• Moreover, LPP displays transcriptional activation capacity, as measured by GAL4-based assays [7].
• The nuclear export of LPP depends on an N-terminally located leucine-rich sequence that shares sequence homology with well-defined nuclear export signals [7].
• Studies utilizing the three-hybrid system further indicated that zyxin and LPP compete for the same binding site in alpha-actinin [8].

Anatomical context of LPP

• All of the LIM domains of LPP cooperate in order to provide robust targeting to focal adhesions, and the linker between LIM domains 1 and 2 plays a pivotal role in this targeting [9].
• LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity [7].
• A corresponding pattern of periodic labeling at the membrane in transverse sections of bladder smooth muscle suggested an association of LPP with peripheral dense bodies [10].
• Overexpression of the protein increased EGF-stimulated migration of vascular smooth muscle cells in Transwell assays, suggesting the participation of LPP in cell motility [10].
• Intrapatellar tendon lipoma with chondro-osseous differentiation: detection of HMGA2-LPP fusion gene transcript [11].

Associations of LPP with chemical compounds

• In addition, LPP accumulates in the nucleus of cells upon treatment with leptomycin B, an inhibitor of the export factor CRM1 [7].
• HPP-CFC were only depleted to 57% of normal at 2 days after FU treatment, whereas the cells responsive to PMUE alone (low proliferative potential, LPP-CFC) were depleted to 1.2%, indicating a marked difference in cycling status of the respective types of progenitor cells [12].
• Addition of appropriate concentrations of PGE1 to the agar culture assay should improve detection of HPP-CFC by inhibiting the proliferation of LPP-CFC [13].
• Rats with an estrogen implant had an LPP of 42.5 +/- 16.8 cm H2O, which was significantly greater than rats given sham implants and significantly less than unoperated controls [14].
• Seven days following nerve crush urethral LPP testing was performed using urethane anesthesia [14].

Physical interactions of LPP

• The lipoma preferred partner LPP interacts with alpha-actinin [8].
• Previously, we established that LPP interacts with the tumor suppressor Scrib, a member of the leucine-rich repeat and PDZ (LAP) family of proteins [15].

Regulatory relationships of LPP

• This deletion may bring the BCL6 gene under the control of regulatory elements of the LPP gene or the miRNA-28 gene located in intron 4 of LPP [16].
• In stented pig coronary vessels, LPP was expressed in the neointima of cells lacking smoothelin and showed expression patterns identical to those of SM alpha-actin [17].

Other interactions of LPP

• Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23) [18].
• LPP localizes in focal adhesions as well as in cell-to-cell contacts, and it binds VASP, a protein implicated in the control of actin organization [7].
• The LPP gene is the preferred translocation partner of the HMGIC gene in a subclass of human benign mesenchymal tumors known as lipomas [7].
• The genomic organization of the ZRP-1 coding sequence is identical to that of the lipoma preferred partner gene, another Zyxin-related protein, suggesting that the two genes have evolved from a recent gene duplication event [19].
• Real-time PCR analysis showed that HMGA2-LPP and COL11A2 were co-expressed [20].

Analytical, diagnostic and therapeutic context of LPP

• Through inverse PCR, the LPP (lipoma preferred partner) gene on 3q28 was identified as the MLL fusion partner [18].
• By RT-PCR and restriction analysis, we have investigated the HMGIC-LPP fusion transcripts in a series of 13 PCHs with t(3;12)(q27-28;q14-q15) [21].
• By fluorescence in situ hybridization we found that both HMGIC and LPP are disrupted by this translocation [22].
• Using a specific anti-LPP antibody, we showed, in Western blots and with immunofluorescence microscopy, the selective expression of LPP in vascular and visceral smooth muscles (approximately 0.5-1 ng/microg total protein) [10].
• RESULTS: Mean LPP +/- SEM was significantly decreased after pudendal nerve crush in sham treated animals compared to unoperated controls (32.1 +/- 6.8 vs 54.4 +/- 11.6 cm H2O) [14].

References