KANSL2 regula la sintesis del rRNA y la proliferacion

CANEDO, LUCIA; MARINA CUENCA; GUILLERMO AGUSTÍN VIDELA RICHARDSON; NICOLAS FURMAN; GUSTAVO MOSTOSLAVSKY; KOBAYASHI, KEN; ESPINOSA, JOAQUIN M.; CAROLINA PEREZ CASTRO

Congreso; Reunion Anual de Sociedades de Biociencias SAIC; 2019

KANSL2/NSL2 is a subunit of the non-specific lethal (NSL) complex which is important for epigenetic regulation of embryonic stem cells. Previously, we reported KANSL2 is enriched in glioblastoma (GBM) tumors and regulates the stem cell subpopulation. Here, we further characterize KANSL2 role in GBM as a way of understanding the mechanisms behind its tumor-promoting activity. We determined that KANSL2 has a heterogeneous subcellular localization with enriched accumulation in nucleoli. The nucleolus hypertrophy has long been considered a marker of tumor malignancy in the clinic, but only recently has been shown to be an active regulator of tumorigenesis and cellular plasticity. We show here KANSL2 regulates ribosomal RNA (rRNA) synthesis in nucleoli. KANSL2-RFP overexpression positively regulated an rDNA-Luc reporter construct in GBM cells whereas KANSL2 knockdown diminished luciferase activity. A similar expression profile was observed for the polymerase I subunit POLR1E and the Upstream binding factor (UBF), both vital for rRNA synthesis. As anticipated from these findings, cellular proliferation was enhanced in KANSL2-RFP transfected cells while KANSL2 knockdown reduced the proliferation. Statistical significance was obtained with a cut-off p-value ≤ 0.05. Our findings indicate KANSL2 is a nucleolar protein that plays role in rRNA biogenesis and cellular proliferation.