STIL (SCL/TAL1 interrupting locus)

2005-10-01   Asher Castiel , Shai Izraeli 

Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel 52621

Identity

HGNC
LOCATION
1p33
LOCUSID
ALIAS
MCPH7,SIL
FUSION GENES

DNA/RNA

Atlas Image
Genomic structure of SIL. EcoRI sites (R) are indicated. Exons are as shown; the smaller exons are not drawn to scale.

Description

18 exons distributed over 70 kb. 5 portion of the gene demonstrating alternate exon utilization.

Proteins

Expression

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

Localisation

Cytosolic protein

Function

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.

Homology

There is no homology to other known proteins.

Mutations

Note

No mutations were found in families with hereditary holoprosencephaly.

Implicated in

Entity name
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 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.
Atlas Image
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.
Entity name
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 cell lines (Dami-acute megakaryocytic, and K562- erythroid 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.

Bibliography

Pubmed IDLast YearTitleAuthors
13112141992Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia.Aplan PD et al
160248012005Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint.Campaner S et al
124387422002Isolation and characterization of a human novel RAB (RAB39B) gene.Cheng H et al
125314812003Cloning and characterization of the SIL promoter.Colaizzo-Anas T et al
151078242004Sil overexpression in lung cancer characterizes tumors with increased mitotic activity.Erez A et al
93722401997Expression of the SIL gene is correlated with growth induction and cellular proliferation.Izraeli S et al
116686812001Genetic evidence that Sil is required for the Sonic Hedgehog response pathway.Izraeli S et al

Other Information

Locus ID:

NCBI: 6491
MIM: 181590
HGNC: 10879
Ensembl: ENSG00000123473

Variants:

dbSNP: 6491
ClinVar: 6491
TCGA: ENSG00000123473
COSMIC: STIL

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000123473ENST00000337817A0A0A0MR87
ENSG00000123473ENST00000360380Q15468
ENSG00000123473ENST00000371877Q15468
ENSG00000123473ENST00000396221E9PSF2
ENSG00000123473ENST00000413565Q5T0C8
ENSG00000123473ENST00000436811H0Y702
ENSG00000123473ENST00000447475Q5T0C7

Expression (GTEx)

0
5
10
15
20
25

References

Pubmed IDYearTitleCitations
220201242011The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation.100
192157322009Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly.90
253420352014Direct interaction of Plk4 with STIL ensures formation of a single procentriole per parental centriole.84
223497052012STIL is required for centriole duplication in human cells.81
223496982012Cell-cycle-regulated expression of STIL controls centriole number in human cells.74
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
240528132013Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly.48
244858342014STIL microcephaly mutations interfere with APC/C-mediated degradation and cause centriole amplification.48
221009142011Spindle positioning in human cells relies on proper centriole formation and on the microcephaly proteins CPAP and STIL.46
261880842015STIL binding to Polo-box 3 of PLK4 regulates centriole duplication.46

Citation

Asher Castiel ; Shai Izraeli

STIL (SCL/TAL1 interrupting locus)

Atlas Genet Cytogenet Oncol Haematol. 2005-10-01

Online version: http://atlasgeneticsoncology.org/gene/524/stil