Novel functions of ribosomal protein S6 in growth and differentiation of Dictyostelium cells

Abstract

We have previously shown that in Dictyostelium cells a 32 kDa protein is rapidly and completely dephosphorylated in response to starvation that is essential for the initiation of differentiation (Akiyama & Maeda 1992). In the present work, this phosphoprotein was identified as a homologue (Dd-RPS6) of ribosomal protein S6 (RPS6) that is an essential member for protein synthesis. As expected, Dd-RPS6 seems to be absolutely required for cell survival, because we failed to obtain antisense-RNA mediated cells as well as Dd-rps6-null cells by homologous recombination in spite of many trials. In many kinds of cell lines, RPS6 is known to be located in the nucleus and cytosol, but Dd-RPS6 is predominantly located in the cell cortex with cytoskeletons, and in the contractile ring of just-dividing cells. In this connection, the overexpression of Dd-RPS6 greatly impairs cytokinesis during axenic shake-cultures in growth medium, resulting in the formation of multinucleate cells. Much severe impairment of cytokinesis was observed when Dd-RPS6-overexpressing cells (Dd-RPS6 OE cells) were incubated on a living Escherichia coli lawn. The initiation of differentiation triggered by starvation was also delayed in Dd-RPS6 OE cells. In addition, Dd-RPS6 OE cells exhibit defective differentiation into prespore cells and spores during late development. Thus, it is likely that the proper expression of Dd-RPS6 may be of importance for the normal progression of late differentiation as well as for the initiation of differentiation.

Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer

“…It has been reported that rpS6 has diverse functions in cellular metabolism as well as protein synthesis [ 6 , 37 , 38 ]. Exceptional expression or activation of rpS6 has been found in multiple sclerosis [ 39 ], pancreatic cancer [ 40 ], squamous cell carcinoma of the oral cavity [ 17 ], and even the brain areas with acute ketamine-induced neuroplasticity [ 41 ].…”

“…Following studies provided more evidence that the depletion of rpS6 was able to cause p53 induced cell cycles checkpoint impeding or arrest [ 50 , 51 ], suggesting the possible molecular mechanisms of rpS6 in cell cycles regulation. Recent researches even ascribed the cell cycles regulation effects to the phosphorylation at the site of Ser240/244 [ 18 , 37 , 52 ]. Although our study differed from the reports in the phosphorylated residues, the fact that rpS6-mediated cell viability was largely related to the cells cycles redistributions was almost believable.…”

Cell‐cycle checkpoint for transition from cell division to differentiation

“…The serine residue(s) of the 32 kDa protein is rapidly and completely dephosphorylated within 30 min of starvation (Akiyama & Maeda 1992). Recently, this phosphoprotein was identified as a homologue (Dd‐RPS6) of ribosomal protein S6 (RPS6) that is an essential member of protein synthesis (Ishii et al. 2009).…”

“…As expected, Dd‐RPS6 is absolutely required for cell survival; we failed to obtain antisense‐RNA mediated cells and Dd‐rps6 ‐null cells by homologous recombination in spite of many trials. Somewhat surprisingly, Dd‐RPS6‐overexpressing cells exhibit the delayed initiation of differentiation triggered by starvation (Ishii et al. 2009).…”