DEDD2

DEDD2 Full Name

death effector domain containing 2

DEDD2 Introduction

DEDD2 is a regulatory protein with a Death Effector Domain (DED) and a member of the DED protein family. The gene that encodes DEDD2 is localized to human chromosome 19q13.2. DEDD2 displays the characteristic modular organization of the family, that is to say a well-conserved N-terminal DED domain (this module is the signature structural element of the family, and is responsible for the protein-protein interaction) and a C-terminal portion bearing several nuclear localization signals (NLS). It is this feature that accounts for the unique subcellular localization of this protein.

Figure 1. Death effector domain containing proteins. (Source: Valmiki MG, et al. 2009)

The core biological function of DEDD2 is primarily exerted through the induction of apoptosis. It has been demonstrated that DEDD2 can strongly potentiate the sensitization of Fas, TRAIL or FADD-mediated extrinsic apoptotic pathway, and can induce the apoptotic program by itself when overexpressed in cells. DEDD2 interacts with members of the caspase family. Via the DED domain it directly binds to and promotes the activation of initiator caspases caspase-8 and caspase-10, and thus serves as an adaptor molecule in the death receptor-initiated apoptotic signaling. The ability of DEDD2 to induce apoptosis is dependent in an absolute manner on its nuclear localization, and integrity of C-terminal NLS region was found to be required for nuclear accumulation and induction of apoptosis. DEDD2 was also found to have the ability to specifically interact with the apoptosis inhibitory protein FLIP, and not to form stable complexes with FADD or caspase-8, and thus selectively regulating the inhibitory activity of FLIP may be another mechanism to control the apoptotic threshold.

DEDD2 is ubiquitously expressed in normal human tissues and cell lines, and is thus most likely a universal part of the basal apoptotic regulatory network, and therefore potentially involved in general cellular homeostasis. The 19q13.2 chromosomal locus in which DEDD2 resides is often affected by chromosomal aberrations in certain human cancers (such as breast cancer), which also suggests a potential as a modifier of the tumor microenvironment. The observed down-regulation and tumor suppressor activity of its homologous protein EDD (the mammalian homolog of DEDD), which is altered in breast cancer, also indirectly suggests an anti-cancer role for DEDD2.

Alternate Names for DEDD2

DEDD2; death effector domain containing 2; FLAME-3; DNA-binding death effector domain-containing protein 2; DED-containing protein FLAME-3; FADD-like anti-apoptotic molecule 3

• 1. Valmiki MG, et al. Death effector domain-containing proteins. Cell Mol Life Sci. 2009 Mar;66(5):814-30.
  2. Lo YC, et al. Tandem DEDs and CARDs suggest novel mechanisms of signaling complex assembly. Apoptosis. 2015 Feb;20(2):124-35.