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Gene Section
Mini Review
LPP (lipoma preferred partner)
Marleen M Petit
Laboratory for Molecular Oncology, Department of Human Genetics, University of Leuven (K.U.Leuven) &
VIB, Herestraat 49, B-3000 Leuven, Belgium (MMP)
Published in Atlas Database: May 2004
Online updated version: http://AtlasGeneticsOncology.org/Genes/LPPID72.html
DOI: 10.4267/2042/38093
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2004 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
DNA/RNA
HGNC (Hugo): LPP
Location: 3q27-q28
Description
At least 11 exons; predicted start codon in exon 3, stop
codon in exon 11; the protein coding region is covered
by the overlapping "CEPH Mark 1" YAC clones
135H6 and 192B10 (start codon in 135H6, stop codon
in 192B10) and is dispersed over at least 400 kb
genomic DNA; the LIM domains are encoded by
separate exons: LIM 1 is encoded by exon 8, LIM 2 by
exon 9, and LIM 3 by exon 10 and part of exon 11.
Transcription
mRNA: ubiquitously: > 10 kb; testis: additional
transcripts of 1.8 kb and 1.25 kb.
Pseudogene
No pseudogenes.
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular
Cytogenetics.
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
204
LPP (lipoma preferred partner)
Petit MM
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 DNAbinding domains of HMGA2 followed by two LIM
domains (LIM 2 and LIM 3) or a portion of the prolinerich region and all three LIM domains of LPP.
Protein
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 VASPbinding 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 cellcell 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.
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 DNAbinding domains of HMGA2 followed by the two most
carboxy-terminal LIM domains (LIM 2 and LIM 3) of
LPP.
Function
Because of their structural features (many proteinprotein 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.
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.
Mutations
Somatic
HMGA2/LPP fusion proteins and MLL/LPP fusion
proteins (Fig2).
Implicated in
Solitary lipomas
Disease
Benign tumors of adipose tissue.
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
205
LPP (lipoma preferred partner)
Petit MM
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 DNAbinding domains of HMGA2 followed by the two most
carboxy-terminal LIM domains (LIM 2 and LIM 3) of
LPP.
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 DNAbinding domains of HMGA2 followed by the two most
carboxy-terminal LIM domains (LIM 2 and LIM 3) of
LPP.
AML-M5
Soft tissue chondroma
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).
Disease
Benign tumor of cartilage; rare entity.
Cytogenetics
Only 31 cases with abnormal karyotypes have been
reported (11-2003); 12q15 nonrandomly involved; one
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
206
LPP (lipoma preferred partner)
Petit MM
fused to MLL in a secondary acute leukemia with a t(3;11)
(q28;q23). Genes Chromosomes Cancer. 2001 Aug;31(4):3829
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 DNAbinding domains and the methyltransferase-like domain
of MLL followed by the two most carboxy-terminal
LIM domains (LIM 2 and LIM 3) of LPP.
Lemke I, Rogalla P, Bullerdiek J. A novel LPP fusion gene
indicates the crucial role of truncated LPP proteins in lipomas
and pulmonary chondroid hamartomas. Cytogenet Cell Genet.
2001;95(3-4):153-6
Dahlén A, Mertens F, Rydholm A, Brosjö O, Wejde J, Mandahl
N, Panagopoulos I. Fusion, disruption, and expression of
HMGA2 in bone and soft tissue chondromas. Mod Pathol.
2003 Nov;16(11):1132-40
References
Gorenne I, Nakamoto RK, Phelps CP, Beckerle MC, Somlyo
AV, Somlyo AP. LPP, a LIM protein highly expressed in
smooth muscle. Am J Physiol Cell Physiol. 2003
Sep;285(3):C674-85
Petit MM, Mols R, Schoenmakers EF, Mandahl N, Van de Ven
WJ. LPP, the preferred fusion partner gene of HMGIC in
lipomas, is a novel member of the LIM protein gene family.
Genomics. 1996 Aug 15;36(1):118-29
Li B, Zhuang L, Reinhard M, Trueb B. The lipoma preferred
partner LPP interacts with alpha-actinin. J Cell Sci. 2003 Apr
1;116(Pt 7):1359-66
Petit MM, Swarts S, Bridge JA, Van de Ven WJ. Expression of
reciprocal fusion transcripts of the HMGIC and LPP genes in
parosteal lipoma. Cancer Genet Cytogenet. 1998 Oct
1;106(1):18-23
Nelander S, Mostad P, Lindahl P. Prediction of cell typespecific gene modules: identification and initial characterization
of a core set of smooth muscle-specific genes. Genome Res.
2003 Aug;13(8):1838-54
Rogalla P, Kazmierczak B, Meyer-Bolte K, Tran KH, Bullerdiek
J. The t(3;12)(q27;q14-q15) with underlying HMGIC-LPP fusion
is not determining an adipocytic phenotype. Genes
Chromosomes Cancer. 1998 Jun;22(2):100-4
Petit MM, Meulemans SM, Van de Ven WJ. The focal adhesion
and nuclear targeting capacity of the LIM-containing lipomapreferred partner (LPP) protein. J Biol Chem. 2003 Jan
24;278(4):2157-68
Petit MM, Fradelizi J, Golsteyn RM, Ayoubi TA, Menichi B,
Louvard D, Van de Ven WJ, Friederich E. LPP, an actin
cytoskeleton protein related to zyxin, harbors a nuclear export
signal and transcriptional activation capacity. Mol Biol Cell.
2000 Jan;11(1):117-29
This article should be referenced as such:
Petit MM. LPP (lipoma preferred partner). Atlas Genet
Cytogenet Oncol Haematol. 2004; 8(3):204-207.
Dahéron L, Veinstein A, Brizard F, Drabkin H, Lacotte L,
Guilhot F, Larsen CJ, Brizard A, Roche J. Human LPP gene is
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
207