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Review
, 11 (2)

Protein Phosphatases-A Touchy Enemy in the Battle Against Glioblastomas: A Review

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Review

Protein Phosphatases-A Touchy Enemy in the Battle Against Glioblastomas: A Review

Arata Tomiyama et al. Cancers (Basel).

Abstract

Glioblastoma (GBM) is the most common malignant tumor arising from brain parenchyma. Although many efforts have been made to develop therapies for GBM, the prognosis still remains poor, mainly because of the difficulty in total resection of the tumor mass from brain tissue and the resistance of the residual tumor against standard chemoradiotherapy. Therefore, novel adjuvant therapies are urgently needed. Recent genome-wide analyses of GBM cases have clarified molecular signaling mechanisms underlying GBM biology. However, results of clinical trials targeting phosphorylation-mediated signaling have been unsatisfactory to date. Protein phosphatases are enzymes that antagonize phosphorylation signaling by dephosphorylating phosphorylated signaling molecules. Recently, the critical roles of phosphatases in the regulation of oncogenic signaling in malignant tumor cells have been reported, and tumorigenic roles of deregulated phosphatases have been demonstrated in GBM. However, a detailed mechanism underlying phosphatase-mediated signaling transduction in the regulation of GBM has not been elucidated, and such information is necessary to apply phosphatases as a therapeutic target for GBM. This review highlights and summarizes the phosphatases that have crucial roles in the regulation of oncogenic signaling in GBM cells.

Keywords: glioblastoma; protein phosphatase; signaling; therapy.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Protein phosphatases in human. Human phosphoprotein phosphatases (PPPs) are classified into two large classes as classical or atypical PPPs. And, these classes of PPPs are further grouped into families or subfamilies based on the amino-acid residue they dephosphorylate or their chemical structure. The PPPs focused in the text are written in red characters. Ser, Serine; Thr, Threonine; Tyr, Tyrosine; PPP, phosphoprotein phosphatase; PP2A, protein phosphatase 2A; PP2B protein phosphatase 2B; PP2C, protein phosphatase 2C; PPM, metal-dependent protein phosphatase; FCP, TFIIF-associating component of RNA polymerase Ⅱ carboxy-terminal domain phosphatase; PTP, protein Tyr phosphatase; LMPTP, low molecular weight PTP; VH1-like DSP [38], Vaccinia virus gene H1-like dual specificity phosphatase; PGAM5, phosphoglycerate mutase family member 5; Sts, suppressor of T-cell receptor signaling; EYA, eyes absent.
Figure 2
Figure 2
Multiple roles of protein phosphatase 2A (PP2A) in the regulation of cell death signaling. PP2A regulates both cell death-inducing and cell survival-inducing signaling simultaneously in not only mitochondria- but p53-dependent cell death cascade. In mitochondria-dependent cell death cascade, PP2A activates both pro-apopototic (Bax and Bad) and anti-apoptotic (Bcl-2 and Bcl-xl) Bcl-2 family proteins simultaneously by dephosphorylation. On the other hand, in p53-dependent cell death cascade, PP2A suppresses p53 inhibitor MDM2 and MDM2 activator Akt as well as p53 and p53 activator Chk1/2. Bcl-2, B cell lymphoma 2; Bcl-xl, B-cell lymphoma extra large; p53, tumor protein p53; Chk1/2, Serine/threonine-protein kinase Chk1/2; MDM2, Mouse double minute 2 homolog; Akt, protein kinase B.

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