Protein inhibitor of activated STAT2

Protein inhibitor of activated STAT2 (PIAS2) is a member of the PIAS (Protein Inhibitor of Activated STAT) family, which plays a crucial role in the regulation of signal transducer and activator of transcription (STAT) proteins. PIAS2 is involved in various cellular processes, including transcriptional regulation, DNA repair, and cell cycle control.

Structure and Function

PIAS2 is a protein that interacts with STAT2, a member of the STAT family of transcription factors. STAT2 is primarily involved in the interferon signaling pathway, which is critical for the immune response to viral infections. PIAS2 inhibits the activity of STAT2 by promoting its sumoylation, a post-translational modification that alters the function and localization of STAT2.

Mechanism of Action

PIAS2 exerts its inhibitory effects on STAT2 through several mechanisms:

• Sumoylation: PIAS2 acts as an E3 SUMO-protein ligase, facilitating the attachment of SUMO (Small Ubiquitin-like Modifier) proteins to STAT2. This modification can inhibit the transcriptional activity of STAT2.
• Transcriptional Repression: PIAS2 can recruit other co-repressors to the STAT2 complex, thereby inhibiting the transcription of STAT2 target genes.
• Subcellular Localization: By promoting the sumoylation of STAT2, PIAS2 can alter the subcellular localization of STAT2, sequestering it away from the nucleus and preventing it from activating target genes.

Biological Significance

The regulation of STAT2 by PIAS2 is essential for maintaining the balance of immune responses. Dysregulation of PIAS2 or STAT2 can lead to various pathological conditions, including autoimmune diseases, viral infections, and cancer. Understanding the role of PIAS2 in STAT2 regulation provides insights into potential therapeutic targets for these diseases.

Related Proteins

PIAS2 is part of a larger family of PIAS proteins, which includes:

• PIAS1
• PIAS3
• PIAS4

Each member of the PIAS family has distinct but sometimes overlapping functions in the regulation of STAT proteins and other transcription factors.

Research and Clinical Implications

Research on PIAS2 has implications for the development of new therapeutic strategies for diseases involving the immune system and cancer. Targeting the interaction between PIAS2 and STAT2 could provide a means to modulate immune responses and inhibit the progression of certain cancers.

See Also

• STAT2
• PIAS family
• Sumoylation
• Interferon signaling pathway
• Transcriptional regulation

External Links

PIAS2
Identifiers
Symbol	PIAS2
NCBI gene	9063
OMIM	603566
RefSeq	NM_006099
UniProt	O75928
Search for Structures Swiss-model Domains InterPro