DFFA - DNA fragmentation factor subunit alpha | Elisa - Clia - Antibody - Protein

Background

DNA Fragmentation Factor Subunit Alpha (DFFA), also known as ICAD (Inhibitor of Caspase-Activated DNase), is a critical protein involved in the regulation of apoptosis. Apoptosis is a programmed cell death process essential for development, tissue homeostasis, and the elimination of damaged or harmful cells. DFFA serves as the regulatory subunit of the DNA Fragmentation Factor (DFF), which also includes the catalytic subunit DFFB (CAD, Caspase-Activated DNase). In healthy cells, DFFA binds to and inhibits DFFB, preventing it from cleaving DNA. During apoptosis, caspases cleave DFFA, releasing DFFB to initiate the fragmentation of chromosomal DNA, a hallmark of apoptosis. DFFA is ubiquitously expressed, reflecting its fundamental role in cellular homeostasis and apoptotic regulation.

Protein Structure

DFFA’s structure includes several domains and motifs that facilitate its regulatory functions:

• N-terminal Domain: This region is involved in the interaction with DFFB, inhibiting its nuclease activity under non-apoptotic conditions.
• Caspase Cleavage Sites: DFFA contains specific sequences recognized and cleaved by caspases during apoptosis. Cleavage at these sites releases the inhibitory grip on DFFB, activating its DNA fragmentation function.
• Nuclear Localization Signals (NLS): These signals direct DFFA to the nucleus, where it can bind to DFFB and regulate its access to chromosomal DNA.

Classification and Subtypes

DFFA is classified within the family of apoptosis regulators, specifically as an inhibitor of DNase activity within the apoptotic pathway:

• DFF Complex: The DFF complex is composed of DFFA and DFFB. DFFA's role as an inhibitory subunit is crucial for controlling the timing and execution of DNA fragmentation during apoptosis.

Function and Biological Significance

DFFA is involved in several critical cellular functions related to apoptosis:

• Regulation of DNA Fragmentation: DFFA inhibits DFFB (CAD) under normal conditions, preventing inadvertent DNA cleavage. Upon apoptotic signaling, caspase-mediated cleavage of DFFA releases and activates DFFB, leading to the fragmentation of DNA.
• Apoptotic Execution: By controlling the activation of DFFB, DFFA plays a key role in the execution phase of apoptosis, ensuring that DNA fragmentation occurs only when cells undergo programmed death.
• Maintenance of Genomic Stability: DFFA's inhibitory function helps maintain genomic stability by preventing accidental DNA damage and fragmentation in healthy cells.

Clinical Issues

Alterations in DFFA function or expression are associated with various diseases:

• Cancer: Dysregulation of apoptosis, including defects in DFFA-mediated inhibition of DNA fragmentation, can contribute to the development and progression of cancer. Cancer cells often evade apoptosis, leading to unchecked proliferation.
• Neurodegenerative Diseases: Abnormal apoptosis and dysregulation of DNA fragmentation are implicated in neurodegenerative diseases. Changes in DFFA function can affect neuronal cell death, contributing to conditions like Alzheimer's and Parkinson's disease.
• Autoimmune Diseases: Proper regulation of apoptosis is critical for immune system homeostasis. Dysregulated DFFA activity can lead to the survival of autoreactive cells, potentially contributing to autoimmune disorders.

Summary

DNA Fragmentation Factor Subunit Alpha (DFFA), also known as ICAD, is a crucial regulatory protein in the apoptosis pathway. It inhibits the catalytic activity of DFFB (CAD) under normal conditions, preventing DNA fragmentation. Upon apoptotic signaling, caspase-mediated cleavage of DFFA releases and activates DFFB, leading to the controlled fragmentation of chromosomal DNA. DFFA's regulatory functions are vital for maintaining genomic stability and ensuring proper execution of apoptosis. Dysregulation of DFFA is associated with cancer, neurodegenerative diseases, and autoimmune conditions. Understanding DFFA's role and regulation is essential for developing therapeutic strategies targeting apoptosis-related diseases.