Suppressor of fused homolog is a protein that in humans is encoded by the SUFU gene. [5] [6] In molecular biology, the protein domain suppressor of fused protein (Sufu) has an important role in the cell. The Sufu is important in negatively regulating an important signalling pathway in the cell, the Hedgehog signalling pathway (HH). This particular pathway is crucial in embryonic development. There are several homologues of Sufu, found in a wide variety of organisms.
SUFU encodes a component of the sonic hedgehog (SHH) / patched (PTCH) signaling pathway. Mutations in genes encoding components of this pathway are deleterious for normal development and are associated with cancer-predisposing syndromes (e.g., holoprosencephaly, HPE3, basal cell nevus syndrome, BCNS, and Greig cephalopolysyndactyly syndrome, GCPS). [6] Sufu has also been found to have a crucial role in tumour suppression. To be more specific, it has a tumour-suppressor gene that predisposes, or in other words makes individuals more susceptible to medulloblastoma, because it modulates the SHH signalling pathway. [7] The N-terminal domain, which this entry refers to contains Gli transcription factors. [8]
SUFU has been shown to interact with GLI1, [9] [10] [11] GLI3 [12] and PEX26. [13]
The human ortholog of Drosophila suppressor of fused, has a conserved sequence, this means that particular amino acids have remained the same throughout evolution. Consequently, they have very similar roles in repressing Hedgehog signalling. It represses the Gli and Ci transcription factors of the Hedgehog pathway, [14] and functions by binding to these proteins and preventing their translocation to the nucleus. Homologues of Sufu have been found in bacteria. However their function remains to be elucidated.
Sufu is actually protein that contains two domains. [8] In eukaryotic Sufu, an additional domain is found at the C terminus of the protein. This protein domain also binds to the C-terminal domain of the Gli/Ci transcription factors, inhibiting their activity. [5]
Human gene that encodes SUFU, also named SUFU, is found to be localized on chromosome 10q24–25, and contains 12 exons. [14]
Sonic hedgehog protein(SHH) is encoded for by the SHH gene. The protein is named after the character Sonic the Hedgehog.
Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells.
Zinc finger protein GLI2 also known as GLI family zinc finger 2 is a protein that in humans is encoded by the GLI2 gene. The protein encoded by this gene is a transcription factor.
Zinc finger protein GLI3 is a protein that in humans is encoded by the GLI3 gene.
Medulloblastoma is a common type of primary brain cancer in children. It originates in the part of the brain that is towards the back and the bottom, on the floor of the skull, in the cerebellum, or posterior fossa.
The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation. Different parts of the embryo have different concentrations of hedgehog signaling proteins. The pathway also has roles in the adult. Diseases associated with the malfunction of this pathway include cancer.
Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine. It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA).
Beta-catenin-interacting protein 1 is a protein that is encoded in humans by the CTNNBIP1 gene.
Protein patched homolog 1 is a protein that is the member of the patched family and in humans is encoded by the PTCH1 gene.
Secreted frizzled-related protein 1, also known as SFRP1, is a protein which in humans is encoded by the SFRP1 gene.
Protein phosphatase 1D is an enzyme that in humans is encoded by the PPM1D gene.
SCL-interrupting locus protein is a protein that in humans is encoded by the STIL gene. STIL is present in many different cell types and is essential for centriole biogenesis. This gene encodes a cytoplasmic protein implicated in regulation of the mitotic spindle checkpoint, a regulatory pathway that monitors chromosome segregation during cell division to ensure the proper distribution of chromosomes to daughter cells. The protein is phosphorylated in mitosis and in response to activation of the spindle checkpoint, and disappears when cells transition to G1 phase. It interacts with a mitotic regulator, and its expression is required to efficiently activate the spindle checkpoint.
Hypermethylated in cancer 1 protein is a protein that in humans is encoded by the HIC1 gene.
HMG-box transcription factor 1, also known as HBP1, is a human protein.
Transcription factor 7 is the gene that in humans encodes for the TCF1 protein.
Metastasis suppressor protein 1 is a protein that in humans is encoded by the MTSS1 gene. True to its name, it codes for a metastasis suppressor.
E3 ubiquitin-protein ligase RNF19A is an enzyme that in humans is encoded by the RNF19A gene.
Zinc finger protein 219 is a protein that in humans is encoded by the ZNF219 gene.
Patched (Ptc) is a conserved 12-pass transmembrane protein receptor that plays an obligate negative regulatory role in the Hedgehog signaling pathway in insects and vertebrates. Patched is an essential gene in embryogenesis for proper segmentation in the fly embryo, mutations in which may be embryonic lethal. Patched functions as the receptor for the Hedgehog protein and controls its spatial distribution, in part via endocytosis of bound Hedgehog protein, which is then targeted for lysosomal degradation.
Patched 2 is a protein that in humans is encoded by the PTCH2 gene.
