Structural highlights
Disease
[STIL_HUMAN] Precursor T-cell acute lymphoblastic leukemia;Autosomal recessive primary microcephaly. 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 slicing 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. The disease is caused by mutations affecting the gene represented in this entry.
Function
[STIL_HUMAN] 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.[1] [2]
Publication Abstract from PubMed
A small number of proteins form a conserved pathway of centriole duplication. In humans and flies, the binding of Plk4/Sak to STIL/Ana2 initiates daughter centriole assembly. In humans, this interaction is mediated by an interaction between the Polo-Box-3 (PB3) domain of Plk4 and the coiled-coil domain of STIL (HsCCD). We showed previously that the Drosophila Ana2 coiled-coil domain (DmCCD) is essential for centriole assembly, but it forms a tight parallel tetramer in vitro that likely precludes an interaction with PB3. Here we show that the isolated HsCCD and HsPB3 domains form a mixture of homo-multimers in vitro, but these readily dissociate when mixed to form the previously described 1:1 HsCCD:HsPB3 complex. In contrast, although Drosophila PB3 (DmPB3) adopts a canonical polo-box fold, it does not detectably interact with DmCCD in vitro Thus, surprisingly, a key centriole assembly interaction interface appears to differ between humans and flies.
A key centriole assembly interaction interface between human Plk4 and STIL appears to not be conserved in flies.,Cottee MA, Johnson S, Raff JW, Lea SM Biol Open. 2017 Feb 15. pii: bio.024661. doi: 10.1242/bio.024661. PMID:28202467[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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):6660-72. PMID:16024801 doi:http://dx.doi.org/10.1128/MCB.25.15.6660-6672.2005
- ↑ 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 Nov;8(11):1171-9. PMID:9372240
- ↑ Cottee MA, Johnson S, Raff JW, Lea SM. A key centriole assembly interaction interface between human Plk4 and STIL appears to not be conserved in flies. Biol Open. 2017 Feb 15. pii: bio.024661. doi: 10.1242/bio.024661. PMID:28202467 doi:http://dx.doi.org/10.1242/bio.024661
