Ubiquitin Specific Peptidase 28 (USP28)

The deduced 1,077-amino acid protein has a calculated molecular mass of 122.4 kD and shares 51.4% identity with USP25. Northern blot analysis detected highest expression of a 4.5-kb transcript in heart and skeletal muscle, with lower expression in all other tissues examined. This transcript contains an extra exon, 19A, that introduces 62 codons into the open reading frame.USP28 was required to stabilize CHK2 and 53BP1 in response to DNA damage. Both USP28 and CHK2 were required for DNA damage-induced apoptosis, and they accomplished this in part through regulation of p53 induction of proapoptotic genes like PUMA. A catalytically-inactive version of USP28, in which the catalytic cysteine (cys171) was changed to alanine, rendered cells resistant to irradiation-induced killing and apoptosis.