Fig. 8: The molecular switch role and mechanism of CDC73 for UBR5-drived TNBC tumor growth and metastasis.
From: UBR5 targets tumor suppressor CDC73 proteolytically to promote aggressive breast cancer
In TNBC cells, CDC73 is stabilized by ERK2-mediated phosphorylation at Ser465. UBR5 targets non-phosphorylated CDC73 (1) and ubiquitinates it at Lys243, Lys247 and Lys257 residues (2) for degradation by UPS (3). Degradation of CDC73 promotes UBR5’s tumorigenic and immunoregulatory activities in TME (4), as well as tumor metastasis in a cell-intrinsic manner by regulating both mRNA and protein expression of β-catenin and E-cadherin (5).
