MDM2 and rheumatoid arthritis: Elevated expression of murine double-minute protein 2 (MDM2), a major negative regulator of p53, is evident in synovial lining of cells in RA [17], and TP53 missense mutations have been documented in intimal and sub-lining regions of RA synovial tissue representing the clonal expansion of cells [18], and these are associated with increased levels of the pro-inflammatory cytokine interleukin-6 (IL-6) [19].