Disease relevance of SUFU

• Mutations in SUFU predispose to medulloblastoma [1].
• Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development [2].
• Four of nine informative fetal rhabdomyomas and embryonal rhabdomyosarcomas showed loss of heterozygosity (LOH) in the PTCH region with two of these (one fetal rhabdomyoma and one embryonal rhabdomyosarcoma) also showing LOH in the SUFU region [2].
• The identification of SUFU mutations in desmoplastic medulloblastoma provides new insights into vertebrate Hedgehog signaling and brain tumor formation [3].
• Targeted disruption of the murine suppressor of fused gene (Sufu) led to a phenotype that included neural tube defects and lethality at mid-gestation (9.0-10.5 dpc) [4].

High impact information on SUFU

• We report here that a subset of children with medulloblastoma carry germline and somatic mutations in SUFU (encoding the human suppressor of fused) of the SHH pathway, accompanied by loss of heterozygosity of the wildtype allele [1].
• Moreover, we have found that a C-terminal 19-amino acid deletion in SUFU (delta465) is sufficient to abrogate interaction with GLI1 [5].
• Coimmunoprecipitation and Far Western assays, coupled with truncation analysis and mutagenesis have been used to define the region of interaction between Gli proteins and SUFU [5].
• A subset of children with MB have germline mutations of SUFU, a known inhibitor of Hedgehog signal transduction [6].
• However, anomalous results obtained with three products (sufu, tempeh, and fully hydrolyzed isolated soy protein) did not make it possible to reach firm conclusions concerning the effect of the protein fraction of soy on iron bioavailability [7].

Biological context of SUFU

• SUFU is a newly identified tumor-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism [1].
• These findings suggest that haploinsufficiency for the two tumour suppressor genes PTCH and SUFU, which are both active in the same signalling pathway, may be important for tumour development [2].
• We uncovered single nucleotide polymorphisms (SNPs) in exon 4, 8, 11 and in intron 2 in the SUFU gene [8].
• All patients with nondesmoplastic medulloblastoma histology received molecular testing for SUFU [9].
• We next identified and characterised CpG islands associated with 5' regions of the MXI1, SUFU and BTRC genes; analysis of these regions for evidence of DNA hypermethylation, alongside expression analysis of their respective transcripts, revealed no evidence to support epigenetic inactivation of any gene [10].

Associations of SUFU with chemical compounds

• A total of 270 isolates were purified and identified by the BBL Crystal Identification System. From the experimental sufu samples, 49 Bacillus spp [11].
• Fermentation temperature did not cause significant differences in the recovery of isoflavones, but resulted in a different redistribution of isoflavone isomers in sufu [12].

Physical interactions of SUFU

• In addition, an in vitro kinase assay showed that GSK3beta phosphorylates Sufu and phosphorylation-mimicking mutant of Sufu showed significantly decreased ability to bind Gli1 and could not suppress the Gli-mediated expression of a reporter gene efficiently [13].

Regulatory relationships of SUFU

• Apparently FU did not have any effect on SUFU induced inhibition of GLI [14].

Other interactions of SUFU

• SMOH mutations were identified in four of the 42 BCCs (10%) while two tumours demonstrated mutations in SUFUH, including one missense mutation and one silent mutation [15].
• These findings implicate the inactivation of critical TS loci at 10q23.3-25.3 in medulloblastoma, however comprehensive analysis of SUFU, BTRC and MXI1 indicates they are unlikely to represent major targets of these allelic losses [10].

Analytical, diagnostic and therapeutic context of SUFU

• Expression analysis by competitive reverse transcription-polymerase chain reaction (RT-PCR) revealed no difference in SUFU mRNA levels of both MB subtypes and normal foetal or adult cerebellar tissues [8].
• Although the longer aging period did not significantly decrease the total bacterial count, it may help in the development of sufu flavor [11].

References