Interruption of ERK and p53 activities decreased SU11274-induced autophagy, and blocking of ERK by the specific inhibitor PD98059 suppressed SU11274-induced p53 activation. Moreover, ERK activation upregulated Beclin-1 expression through induction of Bcl-2 phosphorylation, but p53 did not induce Bcl-2 phosphorylation.

2021年12月4日 · In a word, our results demonstrated that targeting ERK leads to cell death and p53/ROS-dependent protective autophagy simultaneously in colorectal cancer, which offers new potential targets for...

2023年1月31日 · In this study, we reveal that mutant KRAS promotes the formation of the ERK2-p53 complex in stomach/colorectal tumor cells. The three hydrophobic amino acids of the transactivation domain (TAD) of p53 protein are critical for binding with phosphorylated ERK2.

In addition, activation of ERK-p53 and ERK-mediated phosphorylation of Bcl-2 is involved in autophagic cell death in several cancer cell lines, thus indicating that both ROS and p53 can also contribute to simultaneous induction of ERK-induced apoptosis and autophagic cell death.

2007年1月23日 · Abrogation of p53 transactivation activity by pifithrin alpha or dominant-negative mutant of p53 resulted in decrease in activation of ERK in Carb treated cells. The present study for the first time proposes that p53 may act as one of the upstream regulators of ERK activation for the induction of apoptosis in Carb treated cervical cancer cells.

The present study was carried out to determine whether extracellular signal-regulated kinases (ERKs), which are known to be activated by DNA damaging agents, are responsible for doxorubicin-induced p53 activation and oxidative mitochondrial damage in H9c2 cells.

2008年8月7日 · Dominant-negative (DN) p53 genes increased the resistance to chemotherapeutic drugs, MDM-2 and MEK inhibitors, further substantiating the role of p53 in therapeutic sensitivity. The involvement...

2002年4月12日 · Downstream of ATM/ATR lies p53, a central mediator of the response, which in turn induces cell cycle arrest by up-regulation of p21 CIP1 and 14-3-3ς, activates DNA damage repair pathways, and induces apoptosis (5, 6). p53 is normally rapidly degraded by Mdm2-mediated ubiquitin-dependent proteolysis (7, 8).

2004年1月2日 · Here we show that p53 can directly counteract the Ras/MAPK signaling by inactivating ERK2/MAPK. This inactivation is due to a caspase cleavage of the ERK2 protein and contributes to...

In a word, our results demonstrated that targeting ERK leads to cell death and p53/ROS-dependent protective autophagy simultaneously in colorectal cancer, which offers new potential targets for clinical therapy. Colorectal cancer (CRC) is the fourth leading cause of cancer death in the world, with high morbidity and mortality [1, 2].