PPP2R1A

Overview

PPP2R1A is a gene that encodes the alpha isoform of the regulatory subunit A of protein phosphatase 2 (PP2A), a major serine/threonine phosphatase involved in the negative control of cell growth and division. PP2A is a heterotrimeric enzyme composed of a structural A subunit, a catalytic C subunit, and a regulatory B subunit. The A subunit serves as a scaffold for the assembly of the catalytic and regulatory subunits.

Structure

The PPP2R1A gene is located on chromosome 19q13.41 and consists of 15 exons. The protein product of PPP2R1A, the Aα subunit, is a 65 kDa protein that contains 15 HEAT repeats, which are involved in protein-protein interactions. These repeats form a horseshoe-shaped structure that provides a platform for binding the catalytic and regulatory subunits of PP2A.

Function

PPP2R1A plays a critical role in the regulation of various cellular processes, including cell cycle progression, apoptosis, and signal transduction. By dephosphorylating key signaling molecules, PP2A modulates pathways such as the MAPK/ERK pathway, the PI3K/AKT pathway, and the Wnt signaling pathway. The Aα subunit encoded by PPP2R1A is essential for the proper assembly and function of the PP2A holoenzyme.

Clinical Significance

Mutations in PPP2R1A have been implicated in several types of cancer, including ovarian, endometrial, and breast cancers. These mutations often result in the disruption of PP2A function, leading to uncontrolled cell proliferation and tumorigenesis. PPP2R1A mutations are considered driver mutations in certain cancers, making them potential targets for therapeutic intervention.

Research and Therapeutic Implications

Research into PPP2R1A and its role in cancer has led to the exploration of PP2A as a therapeutic target. Strategies to restore PP2A activity in cancer cells include the use of small molecules that stabilize the PP2A holoenzyme or inhibit its negative regulators. Understanding the specific mutations and their effects on PP2A function is crucial for the development of targeted therapies.

Also see

• Protein phosphatase 2
• Serine/threonine phosphatase
• Signal transduction
• Cancer biology
• Chromosome 19 (human)

This medical genetics related article is a stub. You can help WikiMD by expanding it.