The p53 control of apoptosis and proliferation: lessons from Drosophila

Abstract

The canonical role of p53 in preserving genome integrity and limiting carcinogenesis has been well established. In the presence of acute DNA-damage, oncogene deregulation and other forms of cellular stress, p53 orchestrates a myriad of pleiotropic processes to repair cellular damages and maintain homeostasis. Beside these well-studied functions of p53, recent studies in Drosophila have unraveled intriguing roles of Dmp53 in promoting cell division in apoptosis-induced proliferation, enhancing fitness and proliferation of the winner cell in cell competition and coordinating growth at the organ and organismal level in the presence of stress. In this review, we describe these new functions of Dmp53 and discuss their relevance in the context of carcinogenesis.

Fig. 1

The two isoforms of Dmp53. TAD: transactivation domain. DBD: DNA binding domain. OD: oligomerization domain. DΔNp53 is the predominant fly p53 isoform that activates AiP via the induction of mitogens

Fig. 2

Drosophila p53 controls apoptosis, apoptosis-induced proliferation and coordinates organ and systemic growth. (a) In the presence of irreparable cellular damage, Dmp53 activates the Drosophila pro-apoptotic genes: Rpr, Hid, Grim, which in turn inhibit Diap1 activity to activate the caspase-mediate cell death. (b) In the presence of apoptosis, the neighboring cells begin to proliferate to regenerate the damaged tissue. Dmp53 facilitates such apoptosis-induced proliferation by promoting the activation of Wingless (Wg), Decapentaplegic (Dpp) and Notch (N) signaling pathways. (c) Recently, it was discovered that Dmp53 can coordinate organ and systemic growth in the presence of cellular stress or tissue injury. For example, after the developing wing discs are subjected to certain level of irradiation or metabolic stress, the growth of the entire wing disc is delayed in a coordinated fashion to form a final well-proportioned adult wing, and the larval growth and pupariation timing is also delayed to allow the tissues and organ to repair. Dmp53 is required in such organ and system growth coordination through a yet unknown mechanism