CRADD Human

Caspase and RIP Adapter with Death Domain (CRADD), also known as RAIDD (RIP-associated ICH1/CED3-homologous protein with death domain), is a crucial protein involved in the regulation of apoptosis. This protein is encoded by the CRADD gene in humans and plays a significant role in cell death signaling pathways.

CRADD is characterized by its dual-domain structure, which includes an N-terminal caspase recruitment domain (CARD) and a C-terminal death domain (DD). The CARD domain interacts with caspase-2, while the DD interacts with RIPK1 (Receptor-Interacting Protein Kinase 1). This dual-domain structure allows CRADD to act as an adaptor molecule, bridging caspase-2 and RIPK1, thereby facilitating the formation of the PIDDosome complex, which is essential for the activation of caspase-2 and the initiation of apoptosis .

Apoptosis, or programmed cell death, is a vital process in maintaining cellular homeostasis and eliminating damaged or unwanted cells. CRADD plays a pivotal role in this process by recruiting caspase-2 to the cell death signal transduction complex. This complex includes tumor necrosis factor receptor 1 (TNFR1) and RIPK1, which are key components in the apoptosis signaling pathway .

Mutations in the CRADD gene have been associated with various disorders, including intellectual developmental disorder, autosomal recessive 34, and variant lissencephaly. These mutations can disrupt the normal function of CRADD, leading to impaired apoptosis and contributing to the development of these conditions .

CRADD has been extensively studied for its role in apoptosis and its potential implications in cancer research. Understanding the mechanisms by which CRADD regulates cell death can provide valuable insights into the development of therapeutic strategies for cancer and other diseases characterized by dysregulated apoptosis .