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Expression and distribution of PPP2R5C gene in leukemia.

Zheng H, Chen Y, Chen S, Niu Y, Yang L, Li B, Lu Y, Geng S, Du X, Li Y - J Hematol Oncol (2011)

Bottom Line: Significantly higher expression of PPP2R5C was found in AML, CML, T-ALL, and B-CLL groups in comparison with healthy controls.High expression of PPP2R5C was detected in the B-ALL group; however, no significant difference was found compared with the healthy group.The expression level of PPP2R5C in the CML-CR group decreased significantly compared with that in the de novo CML group and was not significantly different from the level in the healthy group.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Hematology, Medical College, Jinan University, Guangzhou, People's Republic of China.

ABSTRACT

Background: Recently, we clarified at the molecular level novel chromosomal translocation t(14;14)(q11;q32) in a case of Sézary syndrome, which caused a rearrangement from TRAJ7 to the PPP2R5C gene. PPP2R5C is one of the regulatory B subunits of protein phosphatase 2A (PP2A). It plays a crucial role in cell proliferation, differentiation, and transformation. To characterize the expression and distribution of five different transcript variants of the PPP2R5C gene in leukemia, we analyzed the expression level of PPP2R5C in peripheral blood mononuclear cells from 77 patients with de novo leukemia, 26 patients with leukemia in complete remission (CR), and 20 healthy individuals by real-time PCR and identified the different variants of PPP2R5C by RT-PCR.

Findings: Significantly higher expression of PPP2R5C was found in AML, CML, T-ALL, and B-CLL groups in comparison with healthy controls. High expression of PPP2R5C was detected in the B-ALL group; however, no significant difference was found compared with the healthy group. The expression level of PPP2R5C in the CML-CR group decreased significantly compared with that in the de novo CML group and was not significantly different from the level in the healthy group. By using different primer pairs that covered different exons, five transcript variants of PPP2R5C could be identified. All variants could be detected in healthy samples as well as in all the leukemia samples, and similar frequencies and distributions of PPP2R5C were indicated.

Conclusions: Overexpression of PPP2R5C in T-cell malignancy as well as in myeloid leukemia cells might relate to its proliferation and differentiation. Investigation of the effect of target inhibition of this gene might be beneficial to further characterization of molecular mechanisms and targeted therapy in leukemia.

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Genomic organization of PPP2R5C. The bars represent the exons, and the lines represent introns. The pink bars are the 5' UTR, the black bars are exons that were identical in all five variants (exons 2-12), the colored bars represent specific exons in different variants, the 3' UTR in different variants is shown with green bars (variants 1, 2, 5 and 6), horizontal-dash-filled pink bars (variant 3), and horizontal-line-filled bars (pseudogene). The coding sequence between exons 2 and 12 and the shown splice junction (downward arrow) were identical across the five splice variants. The location and direction of primers used for amplification of different variants are indicated by arrows [4].
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Figure 1: Genomic organization of PPP2R5C. The bars represent the exons, and the lines represent introns. The pink bars are the 5' UTR, the black bars are exons that were identical in all five variants (exons 2-12), the colored bars represent specific exons in different variants, the 3' UTR in different variants is shown with green bars (variants 1, 2, 5 and 6), horizontal-dash-filled pink bars (variant 3), and horizontal-line-filled bars (pseudogene). The coding sequence between exons 2 and 12 and the shown splice junction (downward arrow) were identical across the five splice variants. The location and direction of primers used for amplification of different variants are indicated by arrows [4].

Mentions: PPP2R5C is one of the regulatory B subunits of protein phosphatase 2A (PP2A), which is a major cellular serine/threonine phosphatase that affects the phosphorylation status of many proteins [4]. The PPP2R5C gene encodes five differentially spliced variants: B56γ1, B56γ2, B56γ3, B56γ5, and B56γ6 (Figure 1), whereas B56γ4 is identified only in mice. The functional PPP2R5C gene locus resides at 14q32.2, whereas a nonfunctional B56γ1 pseudogene PPP2R5C is present at 3p21.3 [4,5]. PPP2R5C plays a crucial role in cell proliferation, differentiation, and transformation, based on its induction of dephosphorylation of P53 at various residues [6]. It has been reported that the dynamic nuclear distribution of the B56γ3 regulatory subunit controls nuclear PP2A activity and may be responsible for the tumor-suppression function of PP2A [5]. Recently, the alteration of the expression pattern of PPP2R5C associated with malignant transformation has been characterized in lung cancer; a PPP2R5C mutation, F395C, disrupts B56γ-p53 interaction [7].


Expression and distribution of PPP2R5C gene in leukemia.

Zheng H, Chen Y, Chen S, Niu Y, Yang L, Li B, Lu Y, Geng S, Du X, Li Y - J Hematol Oncol (2011)

Genomic organization of PPP2R5C. The bars represent the exons, and the lines represent introns. The pink bars are the 5' UTR, the black bars are exons that were identical in all five variants (exons 2-12), the colored bars represent specific exons in different variants, the 3' UTR in different variants is shown with green bars (variants 1, 2, 5 and 6), horizontal-dash-filled pink bars (variant 3), and horizontal-line-filled bars (pseudogene). The coding sequence between exons 2 and 12 and the shown splice junction (downward arrow) were identical across the five splice variants. The location and direction of primers used for amplification of different variants are indicated by arrows [4].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117819&req=5

Figure 1: Genomic organization of PPP2R5C. The bars represent the exons, and the lines represent introns. The pink bars are the 5' UTR, the black bars are exons that were identical in all five variants (exons 2-12), the colored bars represent specific exons in different variants, the 3' UTR in different variants is shown with green bars (variants 1, 2, 5 and 6), horizontal-dash-filled pink bars (variant 3), and horizontal-line-filled bars (pseudogene). The coding sequence between exons 2 and 12 and the shown splice junction (downward arrow) were identical across the five splice variants. The location and direction of primers used for amplification of different variants are indicated by arrows [4].
Mentions: PPP2R5C is one of the regulatory B subunits of protein phosphatase 2A (PP2A), which is a major cellular serine/threonine phosphatase that affects the phosphorylation status of many proteins [4]. The PPP2R5C gene encodes five differentially spliced variants: B56γ1, B56γ2, B56γ3, B56γ5, and B56γ6 (Figure 1), whereas B56γ4 is identified only in mice. The functional PPP2R5C gene locus resides at 14q32.2, whereas a nonfunctional B56γ1 pseudogene PPP2R5C is present at 3p21.3 [4,5]. PPP2R5C plays a crucial role in cell proliferation, differentiation, and transformation, based on its induction of dephosphorylation of P53 at various residues [6]. It has been reported that the dynamic nuclear distribution of the B56γ3 regulatory subunit controls nuclear PP2A activity and may be responsible for the tumor-suppression function of PP2A [5]. Recently, the alteration of the expression pattern of PPP2R5C associated with malignant transformation has been characterized in lung cancer; a PPP2R5C mutation, F395C, disrupts B56γ-p53 interaction [7].

Bottom Line: Significantly higher expression of PPP2R5C was found in AML, CML, T-ALL, and B-CLL groups in comparison with healthy controls.High expression of PPP2R5C was detected in the B-ALL group; however, no significant difference was found compared with the healthy group.The expression level of PPP2R5C in the CML-CR group decreased significantly compared with that in the de novo CML group and was not significantly different from the level in the healthy group.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Hematology, Medical College, Jinan University, Guangzhou, People's Republic of China.

ABSTRACT

Background: Recently, we clarified at the molecular level novel chromosomal translocation t(14;14)(q11;q32) in a case of Sézary syndrome, which caused a rearrangement from TRAJ7 to the PPP2R5C gene. PPP2R5C is one of the regulatory B subunits of protein phosphatase 2A (PP2A). It plays a crucial role in cell proliferation, differentiation, and transformation. To characterize the expression and distribution of five different transcript variants of the PPP2R5C gene in leukemia, we analyzed the expression level of PPP2R5C in peripheral blood mononuclear cells from 77 patients with de novo leukemia, 26 patients with leukemia in complete remission (CR), and 20 healthy individuals by real-time PCR and identified the different variants of PPP2R5C by RT-PCR.

Findings: Significantly higher expression of PPP2R5C was found in AML, CML, T-ALL, and B-CLL groups in comparison with healthy controls. High expression of PPP2R5C was detected in the B-ALL group; however, no significant difference was found compared with the healthy group. The expression level of PPP2R5C in the CML-CR group decreased significantly compared with that in the de novo CML group and was not significantly different from the level in the healthy group. By using different primer pairs that covered different exons, five transcript variants of PPP2R5C could be identified. All variants could be detected in healthy samples as well as in all the leukemia samples, and similar frequencies and distributions of PPP2R5C were indicated.

Conclusions: Overexpression of PPP2R5C in T-cell malignancy as well as in myeloid leukemia cells might relate to its proliferation and differentiation. Investigation of the effect of target inhibition of this gene might be beneficial to further characterization of molecular mechanisms and targeted therapy in leukemia.

Show MeSH
Related in: MedlinePlus