[SCP Phosphatases and Oncogenesis].

Small SCP phosphatases CTDSP1, CTDSP2, and CTDSPL specifically dephosphorylate serine and threonine residues in protein molecules. The enzymes are involved in regulating activity of RNA polymerase II at the transition from transcription initiation to elongation, regulating expression of neuron-specific genes, and activating the key cell-cycle protein pRb at the G1/S boundary. In addition, the substrates of SCP phosphatases include SMAD transcription modulators; AKT1 protein kinase, which regulates the cell cycle, apoptosis, and angiogenesis; the TWIST1 and c-MYC transcription factors; Ras family proteins, which are involved in signaling pathways regulating the cell growth and apoptosis; CDCA3, which is associated with cell division; the cyclin-dependent kinase inhibitor p21; and the promyelocytic leukemia protein (PML), which is involved in regulation of the tumor suppressors p53, PTEN, and mTOR. Dysfunction or inactivation of SCP phosphatases leads to various diseases, including cancer. Recently the increase in interest to SCP phosphatases is due to their their tumor growth-inhibiting properties or role in the development of malignant tumors of various etiology and localization. The review discusses the properties of SCP phosphatases and their role in oncogenesis. Understanding the functions of SCP phosphatases and their regulatory mechanisms can be useful in searching for efficient targets for tumor therapy.

[Differential expression of an ensemble of the key genes involved in cell-cycle regulation in lung cancer].

Targeted cancer therapy directed at individual targets is often accompanied by the rapid development of drug resistance. The development of a new generation of antitumor drugs involves the search for many targets simultaneously to block or, conversely, restore their activity. In this regard, simultaneous analysis of gene expression in a complex network of interactions, primarily cell cycle control elements, is relevant for the search of specific molecular markers for the differential diagnosis of adenocarcinoma (ADC) and squamous cell lung cancer (SCC), as well as new targets for therapy. In this paper we performed an extended quantitative analysis of the expression of two suppressor genes, CTDSPL and its target RB1, as well as 84 genes of the main participants of the p16^(INK4A)-Cdk/cyclin D1-Rb and p53/p21^(Waf1) signaling pathways in the histological types of non-small-cell lung cancer (NSCLC), i.e., ADC and SCC, using the special panel of the Human Cell Cycle Regulation Panel. The expression profile of some genes shows the specificity to the histological type of NSCLC and the presence of metastases. The genes with a significantly increased expression that affect the activity of Rb (cyclins, cyclin-dependent kinases, their activators, inhibitors, etc.) can serve as potential targets for combined therapy of both ADC and SCC.

[Interaction of two tumor suppressors: Phosphatase CTDSPL and Rb protein].

Earlier we established that CTDSPL gene encoding small carboxy-terminal domain serine phosphatase can be considered a classical tumor suppressor gene. Besides, transfection of tumor cell line MCF-7 with CTDSPL led to the content decrease of inactive phosphorylated form of another tumor suppressor, retinoblastoma protein (Rb), and subsequently to cell cycle arrest at the G1/S boundary. This result implied that small phosphatase CTDSPL is able to specifically dephosphorylate and activate Rb protein. In order to add some fuel to this hypothesis, in the present work we studied the interaction of two tumor suppressors CTDSPL and Rb in vitro. GST pool-down assay revealed that CTDSPL is able to precipitate Rb protein from MCF-7 cell extracts, while surface plasmon resonance technique showed that interaction of the two proteins is direct. Results of this study reassert that phosphatase CTDSPL and Rb could be involved in the common mechanism of cell cycle regulation.