Anti-apoptotic proteins in the autophagic world: an update on functions of XIAP, Survivin, and BRUCE

Abstract

X-linked inhibitor of apoptosis protein (XIAP), survivin, and BRUCE are members of the inhibitor-of-apoptosis protein (IAP) family known for their inhibitory effects on caspase activity and dysregulation of these molecules has widely been shown to cause embryonic defects and to promote tumorigenesis in human. Besides the anti-apoptotic functions, recent discoveries have revealed that XIAP, survivin, and BRUCE also exhibit regulatory functions for autophagy in cells. As the role of autophagy in human diseases has already been discussed extensively in different reviews; in this review, we will discuss the emerging autophagic role of XIAP, survivin, and BRUCE in cancer cells. We also provide an update on the anti-apoptotic functions and the roles in maintaining DNA integrity of these molecules. Second mitochondria-derived activator of caspases (Smac) is a pro-apoptotic protein and IAPs are the molecular targets of various Smac mimetics currently under clinical trials. Better understanding on the functions of XIAP, survivin, and BRUCE can enable us to predict possible side effects of these drugs and to design a more "patient-specific" clinical trial for Smac mimetics in the future.

Keywords: Apoptosis; Autophagy; BRUCE; IAP; Smac; Survivin; XIAP.

Fig. 1

Identified binding partners of XIAP

Fig. 2

Schematic diagram showing the interactions between XIAP, survivin, BRUCE, and other molecules in the regulation of cellular autophagy

Fig. 3

The dynamic autophagic environments model

Fig. 4

The chemical structure of different Smac mimetics developed for cancer treatments