Download Gene Section SIL (SCL/TAL1 interrupting locus) Atlas of Genetics and Cytogenetics

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Gene Section
Mini Review
SIL (SCL/TAL1 interrupting locus)
Asher Castiel, Shai Izraeli
Department of Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel-Hashomer,
Ramat Gan, Israel
Published in Atlas Database: October 2005
Online updated version: http://AtlasGeneticsOncology.org/Genes/SILID524ch1p32.html
DOI: 10.4267/2042/38294
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2006 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Expression
Identity
SIL is an immediate early gene, with ubiquitous
expression in proliferating cells and during early
embryonic development. SIL protein levels peak during
mitosis and are degraded on transition to G1. SIL is
phosphorylated in mitosis. It is expressed in multiple
cancers. In lung cancer its expression correlates with
the expression of mitotic checkpoint genes.
Hugo: STIL
Other names: TAL1 (SCL) interrupting locus
Location: 1p32
Local order: UMP-CMPK (47511608-47556531); SIL
(47427869-47491842); TAL1 (47393984-47407363).
Note: 47,427,869 bp from pter; End: 47,491,842 bp
from pter; Size: 63,973 bases; Orientation: minus
strand.
Localisation
Cytosolic protein.
DNA/RNA
Function
Description
SIL knockout mouse embryos die in utero displaying
holopresencephaly, randomized left/right asymmetry
and marked apoptosis of the neural folds. Genetic
evidence showed that SIL is required for the Sonic
Hedgehog response pathway. SIL phosphorylation and
interactions with PIN1 is required for maintenance of
the mitotic checkpoint.
18 exons distributed over 70 kb. 5' portion of the gene
demonstrating alternate exon utilization.
Protein
Description
Homology
1287 amino acids, 148 KDa protein which is highly
conserved in vertebrates only. No homologies to known
protein motifs except for conserved Serin/Threonine
phosporylation sites.
There is no homology to other known proteins.
Genomic structure of SIL. EcoRI sites (R) are indicated. Exons are as shown; the smaller exons are not drawn to scale.
Atlas Genet Cytogenet Oncol Haematol. 2006;10(2)
97
SIL (SCL/TAL1 interrupting locus)
Castiel A, Izraeli S
Schematic representation of SIL/SCL fusion mRNA. The germ line SIL (solid boxes) and SCL (open boxes) genomic structures are
shown. The deletion breakpoints are indicated with arrows. The SIL/SCL genomic rearrangement is indicated
below. The SIL/SCL fusion mRNA is formed by SIL exon 1 (solid box) splicing to SCL exon 3 (open box) in a head-to-tail fashion.
cell lines (Dami-acute megakaryocytic, and K562erythroid blast crisis of chronic myeloid leukemia).
Disease
High expression in non-small cell lung cancer
(NSCLC). In addition, high expression levels in lung
adenocarcinoma, lung squamous carcinoma and lung
small cell carcinoma.
Prognosis
SIL expression is associated with cell proliferation. In
lung cancer, SIL overexpression is correlated with high
mitotic activity.
Mutations
Note: No mutations were found in families with
hereditary holoprosencephaly.
Implicated in
SIL- TAL1 (SCL) fusion
Note: A submicroscopic deletions fuses the promoter
of SIL to TAL1 to induce an abnormal expression of
TAL1.
Disease
T-cell ALL. This TAL1-SIL fusion transcript is found
in approximately 25% of T-ALL patients.
Cytogenetics
Normal karyotype.
Hybrid/Mutated Gene
The promoter region of the SCL gene, a hematopoietic
transcription factor, and the coding region of the SIL
gene are deleted. The molecular result of this SIL/SCL
rearrangement is an interstitial deletion on chromosome
1 that juxtaposes the 5' portion of the SIL gene to the
coding region of the SCL gene. A SIL/SCL fusion
mRNA is produced, with SIL exon 1 splicing to SCL
exon 3 in a head-to-tail fashion. Because these are both
5' untranslated region (UTR) exons, the net result is
that SIL promoter and enhancer elements drive the
expression of a full length SCL gene product.
References
Aplan PD, Lombardi DP, Ginsberg AM, Cossman J, Bertness
VL, Kirsch IR. Disruption of the human SCL locus by
'illegitimate' V-(D)-J recombinase activity. Science 1990 Dec
7;250(4986):1426-1429.
Peter D. Aplan, Donald P. Lombardi, Ilan R. Kirsch. Structural
Characterization of SIL, a Gene Frequently Disrupted in T-Cell
Acute Lymphoblastic Leukemia. Mol Cell Biol 1991
Nov;11(11):5462-5469.
Aplan PD, Lombardi DP, Reaman GH, Sather HN, Hammond
GD, Kirsch IR. Involvement of the putative hematopoietic
transcription factor SCL in T-cell acute lymphoblastic leukemia.
Blood 1992;79(5):1327-1333.
Izraeli S, Colaizzo-Anas T, Bertness VL, Mani K, Aplan PD,
Kirsch IR. Expression of the SIL gene is correlated with growth
induction and cellular proliferation. Cell Growth Differ
1997;8(11):1171-1179.
Izraeli S, Lowe LA, Bertness VL, Good DJ, Dorward DW,
Kirsch IR, Kuehn MR. The SIL gene is required for mouse
embryonic axial development and left-right specification.
Nature 1999 Jun 17;399(6737):691-694.
SIL overexpression in lung cancer
Note: SIL is also overexpressed in various solid tumors
(melanoma, lymphoma, ovary cancer, breast cancer
colon cancer lung and prostate cancer) and leukemic
Atlas Genet Cytogenet Oncol Haematol. 2006;10(2)
Izraeli S, Lowe LA, Bertness VL, Campaner S, Hahn H, Kirsch
IR, Kuehn MR. Genetic evidence that Sil is required for the
Sonic Hedgehog response pathway. Genesis 2001;31(2):7277.
98
SIL (SCL/TAL1 interrupting locus)
Castiel A, Izraeli S
Karkera JD, Izraeli S, Roessler E, Dutra A, Kirsch I, Muenke M.
The genomic structure, chromosomal localization, and analysis
of SIL as a candidate gene for holoprosencephaly. Cytogenet
Genome Res 2002;97(1-2):62-67.
overexpression in lung cancer characterizes tumors with
increased mitotic activity. Oncogene 2004 Jul 8;23(31):53715377.
Campaner S, Kaldis P, Izraeli S, Kirsch IR. Sil phosphorylation
in a Pin1 binding domain affects the duration of the spindle
checkpoint. Mol Cell Biol 2005 Aug;25(15):6660-6672.
Colaizzo-Anas T, P. D. Aplan. Cloning and characterization of
the SIL promoter. Biochim Biophys Acta - Gene Structure and
Expression 2003;1625(2):207-213.
This article should be referenced as such:
Castiel A, Izraeli S. SIL (SCL/TAL1 interrupting locus). Atlas
Genet Cytogenet Oncol Haematol.2006;10(2):97-99.
Erez A, Perelman M, Hewitt SM, Cojacaru G, Goldberg I,
Shahar I, Yaron P, Muler I, Campaner S, Amariglio N, Rechavi
G, Kirsch IR, Krupsky M, Kaminski N, Izraeli S. Sil
Atlas Genet Cytogenet Oncol Haematol. 2006;10(2)
99