The scaffold subunit contains 15 tandem HEAT repeats which arrange to form a horseshoe-like structure that confers remarkable conformational flexibility (Groves, Hanlon, Turowski, Hemmings & Barford, 1999).
CAPPs can be present as the core dimeric enzyme of AC or a trimeric holoenzyme of ABC or AB’C (Janssens & Goris, 2001).
When this binding site is deleted from regulatory proteins, they lose the ability to associate with the catalytic subunit (Egloff et al., 1997).
I1PP2A and I2PP2A inhibit all possible forms of CAPP by associating with the catalytic subunit using their C-terminal domains (Li, Makkinje, & Damuni, 1996).
I2PP2A mainly acts as an inhibitor by binding to the catalytic subunit, causing a conformational change, and rendering it non-functional (Janssens & Goris, 2001).
In the presence of physiological Mn2+ concentrations, I2PP2A can associate with and stimulate the activity of PP1 but Mn2+ does not seem to affect the inhibition of PP2A through I2PP2A, in vitro (Janssens & Goris, 2001).
Studies also show that leukemic fusion proteins can associate with SET and co-immunoprecipitate with CAPP, suggesting that the inhibitory role of I2PP2A may be involved in regulating cell growth in leukemia (Zhu et al., 2006).
In the presence of physiological conditions of Mn2+, I1PP2A can also associate with and stimulate the activity of PP1 but Mn2+ also does not affect the inhibition of PP2A through I1PP2A, in vitro (Janssens & Goris, 2001).
Increased levels of I1PP2A are associated with the regulation of tau proteins, suggesting that CAPP may play a role in Alzheimer’s disease (Wang et al., 2015).
Ceramide is a lipid secondary messenger that has been linked to aspects of the cellular stress response (Janssens & Goris, 2001).
Products of sphingomyelin metabolism, activated by stress, seem to react with sphingolipids to liberate ceramide (Dobrowsky, R.T. 1992).
Sodium selenate increases PP2A activity which decreases tau hyperphosphorylation, indicating that CAPPs may be manipulated to affect brain function (Tan et al., 2016).
AKT inhibition caused by sodium selenate seems to be physiologically effective at low concentrations (Tsukamoto et al., 2013).
The study indicates PP2A activation with theophylline as a method of controlling respiratory inflammation in human airway smooth muscle cells, in vitro (Patel et al., 2016).
It has now been shown that TNFα-mediated ceramide production increases the serine/threonine phosphatase activity of PP1 while insulin does not, indicating a ceramide-specific response (Ghosh et al., 2007).
The generation of ceramide can cause down-regulation of the c-myc gene, which can trigger a cellular cascade resulting in cell death through apoptotic mechanisms (Wolff et al., 1994).
This phosphorylated residue is directly responsible for the apoptotic mechanism of the protein and a dephosphorylation at this site with a CAPP will inhibit its activity (Janssens and Goris, 2001).
This increased activity can be observed with the decreased phosphorylation of MAPK pathway substrates (Janssens & Goris, 2001).
E4orf4, an adenovirus protein that has been shown to induce apoptosis in transformed cells, interacts with ceramide-activated PP2A to have this effect (Janssens & Goris, 2001).
When tau proteins become hyperphosphorylated they dissociate from the microtubules to which they provide stability and are thought to polymerize into neurofibrillary tangles in the brain and contribute to the onset of Alzheimer’s disease (Janssens & Goris, 2001).
The B subunit of a CAPP confers the ability to dephosphorylate hyperphosphorylated tau proteins (Janssens & Goris, 2001).
The α and β isoforms of the scaffold subunit of CAPP have been identified as tumor suppressor genes in skin, lung, breast and colon-derived cell lines (Janssens & Goris, 2001).
The B' regulatory subunit of CAPP also appears to be overexpressed in malignant melanoma, as compared to regular epidermal cells (Janssens & Goris, 2001).
The B' subunit seems to interact specifically with and dephosphorylate paxillin in the focal adhesions of cancer cells (Janssens & Goris, 2001).
When truncated B' γ subunits were expressed in melanoma cells, an increased rate of metastasis was observed (Janssens & Goris, 2001).
It has been shown that ceramide treatment can significantly reduce telomerase production in human lung carcinomas, indicating that CAPPs may be involved in counteracting uncontrolled cell growth (Ogretmen et al., 2001).
A novel monoclonal antibody DC63 reveals that inhibitor 1 of protein phosphatase 2A is preferentially nuclearly localised in human brain.
Theophylline represses IL-8 secretion from airway smooth muscle cells independently of phosphodiesterase inhibition novel role as a protein phosphatase 2A activator.
Sodium selenate, a protein phosphatase 2A activator, mitigates hyperphosphorylated tau and improves repeated mild traumatic brain injury outcomes.
Selenate induces epithelial-mesenchymal transition in a colorectal carcinoma cell line by AKT activation.