SUFU

Description

The SUFU (SUFU negative regulator of hedgehog signaling) is a protein-coding gene located on chromosome 10.

SUFU, or Suppressor of fused homolog, is a protein encoded by the SUFU gene in humans. SUFU plays a crucial role in regulating the Hedgehog signaling pathway (HH), which is essential for embryonic development. It acts as a negative regulator of this pathway, preventing excessive signaling. SUFU is a tumor suppressor gene and mutations in it can lead to medulloblastoma. SUFU interacts with several proteins, including GLI1, GLI3, and PEX26. It is involved in sequestering GLI proteins in the cytoplasm and regulating their activity.

SUFU is a negative regulator in the hedgehog/smoothened signaling pathway. It down-regulates GLI1 and GLI2-mediated transactivation of target genes. It is part of a corepressor complex that acts on DNA-bound GLI1 and may also act by linking GLI1 to BTRC, thereby targeting GLI1 to degradation by the proteasome. SUFU sequesters GLI1, GLI2, and GLI3 in the cytoplasm. This effect is overcome by binding of STK36 to both SUFU and a GLI protein. SUFU is a negative regulator of beta-catenin signaling. It regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) of the full-length form of GLI3 (GLI3FL). GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. When Hh signaling is initiated, SUFU dissociates from GLI3FL and the latter translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A). SUFU is required for normal embryonic development and for the proper formation of hair follicles and the control of epidermal differentiation.

SUFU is also known as BCNS2, JBTS32, PRO1280, SUFUH, SUFUXL.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing