Multi-tasking Sulf1/Sulf2 enzymes do not only facilitate extracellular cell signalling but also participate in cell cycle related nuclear events

• Published in: Experimental cell research Vol. 364; no. 1; pp. 16 - 27
• Main Authors: Krishnakumar, Kavithanjali, Chakravorty, Ishani, Foy, Wendy, Allen, Steve, Justo, Tiago, Mukherjee, Abir, Dhoot, Gurtej K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2018
• Subjects: 60 APPLIED LIFE SCIENCES; CELL CYCLE; CELL DIVISION; CELL MEMBRANES; Cell Nucleus - genetics; Cell Nucleus - metabolism; CELL PROLIFERATION; Cells, Cultured; CULTURE MEDIA; ENZYMES; Extracellular Matrix - metabolism; Glioma - metabolism; Glioma - pathology; Humans; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neurons - cytology; Neurons - metabolism; Nocodazole; Nuclear mobilisation; Signal Transduction; Sulf1; Sulf2; Sulfotransferases - metabolism; Nuclear mobilisation; Nocodazole; Sulf1; Sulf2; Cell cycle
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2018.01.022

This study demonstrates highly dynamic spatial and temporal pattern of SULF1/SULF2 expression in a number of neuronal cell types growing in normal culture medium that included their transient nuclear mobilisation. Their nuclear translocation became particularly apparent during cell proliferation as both SULF1/SULF2 demonstrated not only cell membrane associated expression, their known site of function but also transient nuclear mobilisation during nuclear cell division. Nuclear localisation was apparent not only by immunocytochemical staining but also confirmed by immunoblotting staining of isolated nuclear fractions of C6, U87 and N2A cells. Immunocytochemical analysis demonstrated rapid nuclear exit of both SULF1/SULF2 following cell division that was slightly delayed but not blocked in a fraction of the polyploid cells observed in C6 cells. The overexpression of both Sulf1 and Sulf2 genes in C6 and U87 cells markedly promoted in vitro growth of these cells accompanied by nuclear mobilisation while inhibition of both these genes inhibited cell proliferation with little or no nuclear SULF1/SULF2 mobilisation. SULF1/SULF2 activity in these cells thus demonstrated a clear co-ordination of extracellular cell signalling with nuclear events related to cell proliferation. •Dynamic SULF1/2 mobilisation to nucleus during cell cycle.•SULF1/2 co-ordinate extracellular cell signalling with nuclear role in cell cycle.•SULF1/2 overexpression increases cell proliferation while inhibition reduces growth.