Protein phosphatase 2A (PP2A) regulate critical cell signaling and the human tumor suppressor. PP2A complex that is affected by cancer inhibitor proteins such as protein phosphatase 2A (CIP2A), methylesterase protein phosphatase 1 (PME-1), and nuclear proto-oncogene SET (SET) are frequently deregulated in cancer. However, how they affect the phosphorylation of cellular and how they are redundant in cell regulation are poorly understood. Here, we do phosphoproteomics screen systematically for phospho-targets affected by the depletion of siRNA-mediated CIP2A, PME-1, and SET (for PP2A-enable) or scaffold A-subunit of PP2A (PPP2R1A) (to inhibit PP2A) in HeLa cell.
We identify the target PP2A-modulated in diverse cellular pathways, including kinase signaling, cytoskeleton, RNA splicing, DNA repair, and the nuclear lamina. The results show a non-redundancy between CIP2A, PME-1, and the SET in the regulation of phospho-target. In particular, PP2A inhibition or reactivation affected largely different phosphopeptides, introducing the concept of non-overlapping phosphatase inhibition and activation of responsive site (PIRS and PARS, respectively). This phenomenon is explained by the inhibition of PPP2R1A impact threonines especially dephosphorylated, while the result in the reactivation PP2A dephosphorylation swarming sites and acidophilic.
Using drug-sensitivity of a comprehensive screening in cells PP2A-modulated to evaluate the functional impact of PP2A in cellular pathways vary targeted by these drugs, we find that it is consistent with the effects of phosphoproteome global, modulation of PP2A widely affects the response to more than 200 drug inhibits a broad spectrum of relevant cancer targets. These findings increase our understanding of phosphoproteins, pharmacological responses, and cellular processes regulated by PP2A modulation and can enable the development of combination therapies.
Phosphoproteome and drug response effects mediated by the three ProteinPhosphatase 2A inhibitor proteins CIP2A, SET and PME-1.
Localized Inhibition of Protein Phosphatase one by Nuak one spliceosome Activities and Reveals Increase MYC-Sensitive Input Control of Transcription.
upregulated expression of MYC induces dependence on kinase NUAK1, but the molecular mechanisms underlying this dependence is not yet fully clarified. Here, we show that NUAK1 is predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, nuclear regulatory subunit of PP1, phosphorylated by NUAK1.
Both NUAK1 and PNUTS associate with the splicing machinery. Inhibition NUAK1 abolish the chromatin association of PNUTS, reducing the activity of the spliceosome, and suppress the nascent RNA synthesis. MYC activation does not bypass the requirement for NUAK1 for spliceosome activity but significantly attenuates transcription inhibition. As a result, NUAK1 inhibition in MYC-transformed cells induces the global accumulation both in location RNAPII pauses and the first exon-intron boundary but did not increase mRNA synthesis. We suggest that inhibition of MYC-regulated NUAK1 before RNAPII trap non-productive because of absence of the spliceosome is assembled correctly.
Description: A polyclonal antibody against PPP2R4. Recognizes PPP2R4 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC, IF; Recommended dilution: WB:1:500-1:5000, IHC:1:1000-1:2000, IF:1:50-1:500
Description: Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms.
Description: Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms.
Description: Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms.
Description: A polyclonal antibody against PPP2R4. Recognizes PPP2R4 from Human. This antibody is HRP conjugated. Tested in the following application: ELISA
Description: A polyclonal antibody against PPP2R4. Recognizes PPP2R4 from Human. This antibody is FITC conjugated. Tested in the following application: ELISA
Description: A polyclonal antibody against PPP2R4. Recognizes PPP2R4 from Human. This antibody is Biotin conjugated. Tested in the following application: ELISA
Description: Human PPP2R4 knockdown cell line is engineered by our optimized transduction of the specific shRNA with lentivirus. Knockdown levels are determined via qRT-PCR. Gentaur offers generation of stable knockdown (RNAi) cell lines expressing shRNAs targeting genes of your interest.
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human PPP2R4 (N-Term). This antibody is tested and proven to work in the following applications:
Description: Available in various conjugation types.
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Ca2 + / calmodulin-dependent protein kinase II (CaMKII), governed by the first inhibitor of protein phosphatase 1 (I1PP1), it is very important to maintain cardiovascular homeostasis. However, the role and mechanism I1PP1 to hypoxia-reoxygenation (H / R) injury in cardiomyocytes remains a question. In our study, after I1PP1 excess by adenovirus infection in neonatal cardiomyocytes followed by hypoxia for 4 hours and reoxygenation for 12 hours, alternative splicing CaMKIIδ subtypes, ATP content, and lactate dehydrogenase (LDH) release is determined.
