Interleukin‐9 receptor gene is transcriptionally regulated by nucleolin in T‐Cell lymphoma cells

Abstract

Interleukin-9 (IL-9) is a multifunctional cytokine that not only has roles in immune and inflammatory responses but also is involved in growth-promoting and anti-apoptotic activities in multiple transformed cell lines, which suggests a potential role in tumorigenesis. Over-expression of the receptor of IL-9 (IL-9R) occurs in several types of human leukemias and in radiation-induced mouse T-cell lymphoma (TL). The molecular mechanism that regulates transcription of the IL-9R gene (Il9r) during leukemogenesis is, however, not well understood. Using a mouse TL cell line that has high expression of Il9r, we sought to dissect its promoter structure. Here we show that the active promoter for Il9r is located in the 5'-flanking AT-rich region. Chromatin immunoprecipitation showed the opening of chromatin structure of the promoter region coupled with nucleolin binding in vivo. Immunohistochemical analysis confirmed the increased localization of nucleolin in the nuclei of TL cells. These data indicate that increased expression of Il9r is associated with an increased binding of nucleolin, coupled with chromatin opening, to an AT-rich region in the 5'-flanking region of Il9r in TL cells.

Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

“…The results of the present study demonstrate that the association between P-nucleolin expression and survival status is different from that between P-nucleolin expression and overall survival. Previous studies have demonstrated that nucleolin regulates a number of cancer-associated factors and directly or indirectly participates in tumorigenic pathways (28,29). Therefore, the role of P-nucleolin in cancer should be comprehensively evaluated.…”

Meeting the needs of breast cancer: A nucleolin’s perspective

“…Its predominant localization in the nucleus relates to the fundamental role of this protein in RNA and DNA metabolism 239 . At the intracellular level, nucleolin acts as a transcriptional factor of several oncogenes and provides transcriptional regulation for mRNA of pro-tumorigenic proteins 266,267,269,286,290,291,466 . On the cell-surface, nucleolin has been described as a binding partner for ligands with fundamental roles in tumorigenesis and angiogenesis 240,[303][304][305]318,319 .…”

Decreased serum levels of nucleolin protein fragment, as analyzed by bead-based proteomic technology, in multiple sclerosis patients compared to controls

“…Human nucleolin is a 707-amino acid protein consisting of an acidic histone-like N terminus, a central domain containing four RNA binding domains, and a C terminus that is rich in arginine and glycine. This multidomain structure reflects the diverse roles of nucleolin in cell growth, proliferation and death (Ginisty et al, 1999;Srivastava and Pollard, 1999;Shang et al, 2011). Although nucleolin has been generally considered a predominantly nucleolar protein, it appears to be very mobile and can also be present in the nucleoplasm and cytoplasm and on the cell surface (Daniely and Borowiec, 2000;Wang et al, 2001).…”