APAF1

APAF1

The structure of APAF1 protein.

APAF1 (Apoptotic Peptidase Activating Factor 1) is a protein that plays a crucial role in the initiation of apoptosis, also known as programmed cell death. It is a key component of the apoptosome, a multiprotein complex that activates caspases, the enzymes responsible for executing the apoptotic process. APAF1 is highly conserved across different species, indicating its importance in regulating cell death.

Structure

The APAF1 protein consists of several functional domains that contribute to its role in apoptosis. It contains an N-terminal caspase recruitment domain (CARD), followed by a nucleotide-binding oligomerization domain (NOD), and a C-terminal WD40 repeat domain. The CARD domain is responsible for interacting with caspases, while the NOD domain facilitates the oligomerization of APAF1 molecules. The WD40 repeat domain is involved in protein-protein interactions and is essential for the formation of the apoptosome.

Function

APAF1 functions as an adaptor protein that connects cytochrome c released from the mitochondria to caspases, leading to their activation. Upon receiving apoptotic signals, APAF1 undergoes conformational changes, allowing it to bind to cytochrome c and form the apoptosome. The apoptosome then recruits and activates caspase-9, which subsequently initiates a caspase cascade, resulting in cell death.

Regulation

The activity of APAF1 is tightly regulated to ensure proper control of apoptosis. One of the key regulators of APAF1 is the Bcl-2 family of proteins, which can either promote or inhibit apoptosis. Anti-apoptotic Bcl-2 family members, such as Bcl-2 and Bcl-xL, bind to APAF1 and prevent its activation, thereby blocking apoptosis. On the other hand, pro-apoptotic Bcl-2 family members, such as Bax and Bak, promote APAF1 activation and facilitate apoptosis.

Clinical Significance

Dysregulation of APAF1 has been implicated in various diseases, including cancer and neurodegenerative disorders. In cancer, APAF1 downregulation or inactivation can contribute to the evasion of apoptosis, allowing cancer cells to survive and proliferate uncontrollably. Conversely, APAF1 overexpression has been observed in certain neurodegenerative diseases, leading to excessive apoptosis and neuronal cell death.

See Also

• Apoptosis
• Caspases
• Bcl-2 family