A masked initiation region in retinoblastoma protein regulates its proteasomal degradation

• DOI: 10.1038/s41467-020-16003-3
• Publication Date: 2020-04-24T10:27:15Z
• Authors: Takuya Tomita; Jon M. Huibregtse; Andreas Matouschek
• Keywords: Retinoblastoma protein; E2F; Retinoblastoma; Proteolysis; Cleavage (geology); Protein Degradation

Abstract Retinoblastoma protein (Rb) is a tumor suppressor that binds and represses E2F transcription factors. In cervical cancer cells, human papilloma virus (HPV) E7 to Rb, releasing it from promote cell cycle progression, inducing ubiquitination of Rb. E7-mediated proteasomal degradation Rb requires action by another protease, calpain, which cleaves after Lys 810. However, not clear why cleavage required for degradation. Here, we report the proteasome cannot initiate efficiently on full-length Calpain exposes region recognized proteasome, leading rapid proteolysis These findings identify mechanism regulating stability controlling initiation provide better understanding molecular underlying transformation HPV.