The p53-dependent RR small subunit (p53R2) protein, a newly identified member of the ribonucleotide reductase family, plays a key role in the p53-dependent cellular response to DNA. Several recent studies have suggested that p53R2 also plays an important role in suppressing the invasive potential of human cancer cells. However, the cellular mechanism that regulates invasiveness remains largely unknown. In this study, we show that p53R2 interacts with MEK2 (extracellular signal-regulated kinase (ERK) kinase 2-mitogen-activated protein kinase (MAPK) kinase 2), the molecule immediately upstream of ERK in the Ras-Raf-MAPK signaling cascade. In co-immunoprecipitation and immunofluorescence analyses, we found that p53R2 and MEK2 interact physically in cultured mammalian cells, and that the p53R2 segment comprising amino acids 161-206 is critical for this interaction. Moreover, serum-induced phosphorylation of MEK1/2 and ERK1/2 was greatly augmented in human cancer cells expressing small-interfering RNA against p53R2. On the other hand, phosphorylation of MEK1/2 and ERK1/2 in human cancer cells was markedly attenuated by overexpression of p53R2. Furthermore, MEK2 was required for p53R2 knockdown-induced enhancement of the invasive ability and anchorageindependent growth of human lung cancer H1299 cells. Taken together, these findings show that p53R2 negatively modulates serum-induced MEK-ERK activity and inhibits the MEK-ERK-mediated malignancy potential of human cancer cells.

Background Peri-appendiceal inflammation (PAI) is often found in patients with left-sided ulcerative colitis (UC) or proctitis. However, there is still no consensus on the clinical significance of PAI. This study aimed to identify the clinical significance of PAI in UC as a prognosis factor. Methods We retrospectively collected medical records and endoscopic results of patients with diagnosed left side UC or proctitis between January 2013 and December 2021. According to the presence of PAI, we divided the patients into PAI and non-PAI groups. Demographic features and clinical course of the two groups were collected and analyzed. Results A total of 107 patients (41 of left site UC, 56 of proctitis) were enrolled, of which 52 were in the PAI group and 55 were in the non-PAI group There was no difference in most of the demographic and clinical variables between the PAI and non-PAI groups. During the follow-up period of 51 months for the PAI group and 46 months for the non-PAI group, respectively, there was no difference in disease relapse rate (47.1% vs 49.1%, p=0.823), cumulative rate of disease relapse at 1, 3, and 5 years (10.7%, 26.2%, 34.8% vs 8.39%, 23.0%, 36.7%, p=0.823), rate of treatment escalation (59.6% vs 41.8%, p=0.066) and proximal disease extension (25% vs 25.5%, p=0.957) however, new occurrence of PAI during the follow-up period in the non-PAI group was associated with proximal disease extension (55.6% vs 19.6%, p=0.037) In this study, oral 5-aminosalicylate (ASA) was administered to most patients regardless of the extent of the disease. In patients with proctitis with PAI, oral 5-ASA did not affect relapse rate (37.1% vs 66.7%, p=0.550) and proximal disease extension rate (28.6% vs 33.3%, p=1.000). Conclusion PAI at diagnosis did not affect the course of the disease nor did oral 5-ASA in proctitis, however new occurrences of PAI during follow-up were associated with proximal disease extension.