What is the biological significance of PML expression?
The PML protein contains a number of distinct domains. The RING, B1 B-box and B2 B-box are cysteine-rich, zinc-binding domains primarily involved in protein-protein interactions and do not appear to directly bind nucleic acid.24 These three domains, together with the adjacent leucine-rich coiled coils form the RBCC motif of the PML protein. Studies with PML proteins containing mutations within this motif show that an intact RBCC motif is required for PML’s physiological function as a negative growth regulator.10,12,14,31 Instead of manipulating global gene expression PML appears to only regulate the expression of specific genes. Total protein synthesis, as indicated by 35S-methionine incorporation into cell cultures, is unaffected by PML overexpression.31 However, overexpressed PML has been shown by two independent groups to specifically regulate the expression of cyclin D1, a gene involved in cellular growth.13,14,31 Consistent with its role as a negative growth regulator, PML specifi
