STIL
Function
Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1 (PubMed:16024801, PubMed:9372240). Plays an important role in the regulation of centriole duplication. Required for the onset of procentriole formation and proper mitotic progression. During procentriole formation, is essential for the correct loading of SASS6 and CENPJ to the base of the procentriole to initiate procentriole assembly (PubMed:22020124). In complex with STIL acts as a modulator of PLK4-driven cytoskeletal rearrangements and directional cell motility (PubMed:29712910, PubMed:32107292).
Involvement in disease
A chromosomal aberration involving STIL may be a cause of some T-cell acute lymphoblastic leukemias (T-ALL). A deletion at 1p32 between STIL and TAL1 genes leads to STIL/TAL1 fusion mRNA with STIL exon 1 splicing to TAL1 exon 3. As both STIL exon 1 and TAL1 exon 3 are 5'-untranslated exons, STIL/TAL1 fusion mRNA predicts a full-length TAL1 protein under the control of the STIL promoter, leading to inappropriate TAL1 expression. In childhood T-cell malignancies (T-ALL), a type of defect such as STIL/TAL1 fusion is associated with a good prognosis. In cultured lymphocytes from healthy adults, STIL/TAL1 fusion mRNA may be detected after 7 days of culture.
Microcephaly 7, primary, autosomal recessive
MCPH7
A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals have mild to severe intellectual disability. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Ubiquitinated.
Phosphorylated following the activation of the mitotic checkpoint.
Tissue Specificity
Expressed in all hematopoietic tissues and cell lines. Highly expressed in a variety of tumors characterized by increased mitotic activity with highest expression in lung cancer.
Cellular localization
- Cytoplasm
- Cytosol
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Centriole
- Cytoplasm
- Cell cortex
- Localizes at the leading edge.
Alternative names
SIL, STIL, SCL-interrupting locus protein, TAL-1-interrupting locus protein