Cell death in disease: from 2010 onwards

Abstract

The strong interest in cell death, and the shift in emphasis from basic mechanisms to translational aspects fostered the launch last year of the new sister journal of Cell Death and Differentiation, named Cell Death and Disease, to reflect its stronger focus towards clinical applications. Here, we review that first year of activity, which reflects an enthusiastic response by the scientific community. On the basis of this, we now launch two novel initiatives, the start of a new section dedicated to cancer metabolism and the opening of a new editorial office in Shanghai.

Figure 1

The p53 family in the DNA damage response and cell death regulation. (a) DNA damage and replicative stress can trigger a DNA damage response that involves the function of p53 to regulate cell cycle arrest or apoptosis. During the absence or functional inactivation of p53, the two p53 family members p63 and p73 can at least partially substitute this role through distinct upstream regulators, but with the same biological effect. (b) The protein stability of p53 is mainly regulated by mdm2, whose interaction with p53 can be inhibited by specific low molecular compounds, currently in clinical trials, leading to restoration of p53 steady state protein levels and function. (c) Similarly, the degradation of p63 and p73 is mainly regulated by the ubiquitin E3 ligase ITCH, which offers also a novel therapeutic target. ITCH, in mediating its activity, undergoes a conformational modification in the C-terminal portion (WWP1/AIP5 versus E6AP) in a specific hinge region