Non-syndromic hearing impairment protein 5 is a protein that in humans is encoded by the DFNA5 gene. Hearing impairment is a heterogeneous condition with over 40 loci described. The protein encoded by this gene is expressed in fetal cochlea, however, its function is not known. Nonsyndromic hearing impairment is associated with a mutation in this gene. The observation that DFNA5 is epigenetically inactivated in a large number of cancers of frequent types (gastric, colorectal, and breast) is another important finding and is in line with its apoptosis-inducing properties. Indeed, if apoptosis is an intrinsic feature of DFNA5, shutting the gene down in tumor cells makes them more susceptible to uncontrolled cellular growth. Moreover, the fact that DFNA5 is regulated by P53 strongly suggests that DFNA5 is a tumor suppressor gene.
Background References
1. Rogers C. et. al. Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat. Commun. 8:14128-14128(2017).
2. Van Rossom S. et. al. The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways. Front. Cell. Neurosci. 9:231-231(2015).
Sequence Similarity
Belongs to the gasdermin family.
Tissue Specificity
Expressed in cochlea. Low level of expression in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas, with highest expression in placenta.
Post-translational Modification
Cleavage at Asp-270 by CASP3 (mature and uncleaved precursor forms) relieves autoinhibition and is sufficient to initiate pyroptosis.
Western blot analysis of DFNA5 / GSDME on different lysates with Mouse anti-DFNA5 / GSDME antibody (EM1901-49) at 1/2,000 dilution.
Lane 1: HeLa cell lysate Lane 2: SW480 cell lysate (negative) Lane 3: SGC-7901 cell lysate Lane 4: MCF7 cell lysate (negative) Lane 5: SH-SY5Y cell lysate
Lysates/proteins at 20 µg/Lane.
Predicted band size: 55 kDa Observed band size: 55 kDa
Exposure time: 3 minutes; ECL: K1802;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (EM1901-49) at 1/2,000 dilution was used in 5% NFDM/TBST at 4℃ overnight. Goat Anti-Mouse IgG - HRP Secondary Antibody (HA1006) at 1/50,000 dilution was used for 1 hour at room temperature.
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