PDCD6IP

PDCD6IP Full Name

programmed cell death 6 interacting protein

PDCD6IP Introduction

Programmed cell death 6-interacting protein (PDCD6IP), also known as ALIX, is a cytoplasmic adaptor protein that is expressed in all human tissues. It is most widely known for its involvement in membrane remodeling, a process to which it directly contributes through interaction with the ESCRT (endosomal sorting complexes required for transport) machinery. PDCD6IP has a Bro1 domain and proline-rich domains, which confer the ability to have many binding partners. Thus the protein is involved in many processes such as cytokinesis, endosomal trafficking and apoptosis. PDCD6IP has been implicated in cell survival, with evidence showing that it binds to PDCD6 to permit a calcium-dependent signaling response to stress.

Figure 1. Subnetwork of ALG-2 and interacting proteins in the ESCRT system.(Source: Maki M, et al.; 2016)

Functionally, PDCD6IP has been implicated in multivesicular body biogenesis/exosome formation and in the regulation of membrane scission. Via its interactome, the protein also has an impact on degradation/recycling of membrane receptors, modulation of budding of various enveloped viruses and regulation of cellular homeostasis via autophagy. PDCD6IP has been implicated in actin cytoskeleton dynamics and abscission at the final stage of cell division. This spectrum of functions attests to PDCD6IP's critical role as a regulatory hub to coordinate membrane curvature, vesicle trafficking and stress-related signaling.

Abnormal expression of PDCD6IP has also been linked to the progression of several human diseases. In oncology, PDCD6IP dysregulation in tumor cells has been observed in cancer, including as a driver of tumor growth and metastasis and resistance to therapy. In particular, the role of PDCD6IP in the exosome secretion of breast cancer cells and in regulating apoptosis is thought to contribute to tumor cell growth. In infectious disease, PDCD6IP was found to be used by HIV and Ebola virus to promote viral budding. PDCD6IP is thus considered a host factor that is relevant for progression of viral infections. In neurological disease, particularly neurodegeneration, several studies have suggested that defects in PDCD6IP-mediated autophagy and/or membrane trafficking in neurons may contribute to disease progression by affecting vesicle dynamics, leading to protein aggregation and neurotoxic stress.

Alternate Names for PDCD6IP

PDCD6IP; programmed cell death 6 interacting protein; AIP1; ALIX; HP95; DRIP4; programmed cell death 6-interacting protein; PDCD6-interacting protein; ALG-2 interacting protein 1; ALG-2-interacting protein X; dopamine receptor interacting protein 4; apoptosis-linked gene 2-interacting protein X;

• 1. Maki M, et al.; Multifaceted Roles of ALG-2 in Ca(2+)-Regulated Membrane Trafficking. Int J Mol Sci. 2016, 17(9):1401.