| Description | 612 amino acids; proline-rich region (amino-terminal 2/3 of the protein) followed by three LIM domains (carboxy-terminal 1/3 of the protein). Proline-rich region contains an alfa-actinin binding site, two VASP-binding motifs, and a nuclear export signal. |
| Expression | Smooth muscle marker; readily detected on Western blot with an LPP-antibody in all fibroblastic and epithelial cell lines tested to date. |
| Localisation | LPP is present in the cytoplasm of cells as well as at sites of cell adhesion such as focal adhesions (attachments sites to the extracellular matrix) and cell-cell contacts; LPP also shuttles to the nucleus and its nuclear-cytoplasmic localisation is regulated in part by a nuclear export signal (NES) which is sensitive to the drug leptomycin B. |
| Function | Because of their structural features (many protein-protein interaction domains) and their characteristic to shuttle between the nucleus and the cytoplasm, LPP and its family members (see below) have been proposed to be scaffolding proteins involved in signal transduction from sites of cell adhesion to the nucleus; LPP has been shown to harbour transcriptional activation capacity in luciferase reporter assays, suggesting that LPP may be directly involved in the regulation of gene expression; LPP was found to be highly expressed in smooth muscle, and a role for LPP in regulating cell motility was proposed; the precise function of LPP remains to be elucidated. |
| Homology | LPP is a member of the zyxin family of proteins, which contains five members: ajuba, LIMD1, LPP, TRIP6 and zyxin. The family hallmark of these proteins are three clustered LIM domains at the carboxy-terminus, which are protein interaction domains. All family members are present at sites of cell adhesion and have the ability to shuttle to the nucleus, and all family members have one or more nuclear export signals. |
| Entity | solitary lipomas |
| Disease | Benign tumors of adipose tissue. |
| Prognosis | Can be surgically removed with no recurrence in most cases. |
| Cytogenetics | More than 60% of solitary lipomas have an aberrant karyotype; 2/3 of these carry 12q15 rearrangements, most often translocations, affecting the HMGA2 gene; 1/4 of the latter have chromosomal region 3q27-q28 (containing LPP) as 12q15 translocation partner as such creating an HMGA2/LPP fusion gene. |
| Hybrid/Mutated Gene | HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 8-11 or 9-11 of LPP; under the regulation of the HMGA2 promoter. |
| Abnormal Protein | HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by two LIM domains (LIM 2 and LIM 3) or a portion of the proline-rich region and all three LIM domains of LPP. |
| |  |
| |
| | |
| Entity | Pulmonary chondroid hamartomas |
| Disease | Benign mesenchymal tumors of the lung. |
| Prognosis | good |
| Cytogenetics | More than 70% of pulmonary chondroid hamartomas have an aberrant karyotype; 70% of these carry 12q15 rearrangements, most often translocations, affecting the HMGA2 gene; 1/8 of the latter have chromosomal region 3q27-q28 (containing LPP) as 12q15 translocation partner as such creating an HMGA2/LPP fusion gene. |
| Hybrid/Mutated Gene | HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter. |
| Abnormal Protein | HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP. |
| | |
| Entity | Parosteal lipoma |
| Disease | Rare deep-seated benign tumor of adipose tissue comprising less than 0.5% of all lipomas; parosteal lipomas exhibit a contiguous relationship with the periostium; because of their intimate relationship to the bone, they are considered as lipomas of bone. |
| Prognosis | Most often asymptomatic; in some cases: loss of motor and/or sensory function as a result of the compression or stretching of a nerve. |
| Cytogenetics | One case reported with rearrangement of LPP t(3;12)(q28;q14). |
| Hybrid/Mutated Gene | HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter. |
| Abnormal Protein | HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP. |
| | |
| Entity | Soft tissue chondroma |
| Disease | Benign tumor of cartilage; rare entity. |
| Cytogenetics | Only 31 cases with abnormal karyotypes have been reported (11-2003); 12q15 nonrandomly involved; one case reported with rearrangement of LPP t(3;12)(q27;q15). |
| Hybrid/Mutated Gene | HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter. |
| Abnormal Protein | HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP. |
| | |
| Entity | AML-M5 |
| Disease | Secondary leukemia following treatment with DNA topoisomerase II inhibitors. |
| Cytogenetics | MLL gene on 11q23 frequently involved; one case reported with rearrangement of LPP t(3;11)(q28;q23). |
| Hybrid/Mutated Gene | MLL/LPP hybrid gene containing the first 8 exons of MLL and exons 9-11 of LPP; under the regulation of the MLL promoter. |
| Abnormal Protein | MLL/LPP fusion transcripts encode the three DNA-binding domains and the methyltransferase-like domain of MLL followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP. |
| | |
| LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family. |
| Petit MM, Mols R, Schoenmakers EF, Mandahl N, Van de Ven WJ |
| Genomics. 1996 ; 36 (1) : 118-129. |
| PMID 8812423 |
| |
| Expression of reciprocal fusion transcripts of the HMGIC and LPP genes in parosteal lipoma. |
| Petit MM, Swarts S, Bridge JA, Van de Ven WJ |
| Cancer genetics and cytogenetics. 1998 ; 106 (1) : 18-23. |
| PMID 9772904 |
| |
| The t(3;12)(q27;q14-q15) with underlying HMGIC-LPP fusion is not determining an adipocytic phenotype. |
| Rogalla P, Kazmierczak B, Meyer-Bolte K, Tran KH, Bullerdiek J |
| Genes, chromosomes & cancer. 1998 ; 22 (2) : 100-104. |
| PMID 9598796 |
| |
| LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity. |
| Petit MM, Fradelizi J, Golsteyn RM, Ayoubi TA, Menichi B, Louvard D, Van de Ven WJ, Friederich E |
| Molecular biology of the cell. 2000 ; 11 (1) : 117-129. |
| PMID 10637295 |
| |
| Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23). |
| Dahron L, Veinstein A, Brizard F, Drabkin H, Lacotte L, Guilhot F, Larsen CJ, Brizard A, Roche J |
| Genes, chromosomes & cancer. 2001 ; 31 (4) : 382-389. |
| PMID 11433529 |
| |
| A novel LPP fusion gene indicates the crucial role of truncated LPP proteins in lipomas and pulmonary chondroid hamartomas. |
| Lemke I, Rogalla P, Bullerdiek J |
| Cytogenetics and cell genetics. 2001 ; 95 (3-4) : 153-156. |
| PMID 12063392 |
| |
| Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas. |
| Dahln A, Mertens F, Rydholm A, Brosj O, Wejde J, Mandahl N, Panagopoulos I |
| Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2003 ; 16 (11) : 1132-1140. |
| PMID 14614053 |
| |
| LPP, a LIM protein highly expressed in smooth muscle. |
| Gorenne I, Nakamoto RK, Phelps CP, Beckerle MC, Somlyo AV, Somlyo AP |
| American journal of physiology. Cell physiology. 2003 ; 285 (3) : C674-C685. |
| PMID 12760907 |
| |
| The lipoma preferred partner LPP interacts with alpha-actinin. |
| Li B, Zhuang L, Reinhard M, Trueb B |
| Journal of cell science. 2003 ; 116 (Pt 7) : 1359-1366. |
| PMID 12615977 |
| |
| Prediction of cell type-specific gene modules: identification and initial characterization of a core set of smooth muscle-specific genes. |
| Nelander S, Mostad P, Lindahl P |
| Genome research. 2003 ; 13 (8) : 1838-1854. |
| PMID 12869577 |
| |
| The focal adhesion and nuclear targeting capacity of the LIM-containing lipoma-preferred partner (LPP) protein. |
| Petit MM, Meulemans SM, Van de Ven WJ |
| The Journal of biological chemistry. 2003 ; 278 (4) : 2157-2168. |
| PMID 12441356 |
| |
