A Higher Level of Expression of the Nucleolar Protein SURF6 in Human Normal Activated Lymphocytes and in Lymphocytes of
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HEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
A Higher Level of Expression of the Nucleolar Protein SURF6 in Human Normal Activated Lymphocytes and in Lymphocytes of Patients with Lymphoproliferative Disorders A. A. Moralevaa, M. A. Malyshevaa, S. V. Khajdukova, and O. V. Zatsepinaa,* Presented by Academician O.A. Dontsova Received June 16, 2020; revised June 29, 2020; accepted June 29, 2020
Abstract— Proliferation of mammalian cells is often accompanied by an increase in the content of the nucleolar proteins, which allows researchers to consider such proteins as potential activation markers. To test this assumption experimentally, we examined the expression pattern of the nucleolar rRNA processing factor SURF6 in normal (resting) peripheral blood lymphocytes, lymphocytes activated for proliferation in vitro, and in blood samples from patients with lymphoproliferative diseases. Using two methods (immunofluorescence and immunoblotting), we for the first time showed that the SURF6 protein is not detected in normal lymphocytes but can easily be visualized in lymphocytes after PHA activation and in lymphocytes of lymphocytic leukemia patients. The level of SURF6 expression in patients correlated with the aggressiveness of the disease development determined by the content of Ki-67-positive lymphocytes. These results allow the SURF6 nucleolar protein to be considered as a putative activation marker of lymphocytes in human blood disorders. Keywords: nucleolus, SURF6, lymphocytes, PHA-activation, lymphocytic leukemia DOI: 10.1134/S1607672920050099
The nucleolus is the key cellular organelle for the formation of ribosomes. As a rule, the nucleoli have an increased functional activity in tumor cells, which allows them to meet the higher requirements of proliferating cells for protein synthesis. It is well known that the activation of nucleoli is accompanied by an increase in their size and protein content [1, 2]. These phenotypic features of the nucleoli are used in clinical practice to assess the proliferative potential of malignant transformed cells [3]. Today, the main marker of human cell proliferation is the nucleolar protein Ki67, the known functions of which are associated with the biogenesis of ribosomes and the organization of chromatin and which, for yet unknown reasons, marks cells at the stage of DNA replication (i.e., in the S phase of the cell cycle) [4]. However, the development of personalized medicine and the necessity for more accurate diagnostics of tumors of different etiology require the search for additional activation markers of tumor cells. In oncohematology, nucleolar proteins NPM1 (B23, nucleophosmin) and nucleolin (C23) have been proposed as such markers. However, unlike a Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia *e-mail: [email protected]
Ki-67, these proteins are present in the nucleoli of not only tumor cells but also in many normal cells, which makes it difficult to assess the pool of pathological lymphocytes by the conventional me
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