Drosophila S6 Kinase: A Regulator of Cell Size

Abstract

Cell proliferation requires cell growth; that is, cells only divide after they reach a critical size. However, the mechanisms by which cells grow and maintain their appropriate size have remained elusive. Drosophila deficient in the S6 kinase gene (dS6K) exhibited an extreme delay in development and a severe reduction in body size. These flies had smaller cells rather than fewer cells. The effect was cell-autonomous, displayed throughout larval development, and distinct from that of ribosomal protein mutants (Minutes). Thus, the dS6K gene product regulates cell size in a cell-autonomous manner without impinging on cell number.

Early loss of mammalian target of rapamycin complex 1 (mTORC1) signalling and reduction in cell size during dominant-negative suppression of hepatic nuclear factor 1-α (HNF1A) function in INS-1 insulinoma cells

“…Loss of S6k1 in Drosophila is semi-lethal, and a markedly reduced body size was seen in the surviving adults [36]. This reduction in body size was caused by a decrease in cell size rather than a decrease in the actual cell number [36]. In mice, deletion of S6k1 was not shown to be lethal; however, the S6k1-deficient animals had a significantly reduced birthweight.…”

“…Targets of S6K1 other than ribosomal protein S6 have been identified, such as the transcription factor cAMP responsive element modulator (CREM)-τ, the RNA splicing/export factor cap binding protein 80 (CBP80) and the eukaryotic translation elongation factor 2 (eEF2) [35], which may mediate additional activities of S6K1 that were hitherto partially unknown. Loss of S6k1 in Drosophila is semi-lethal, and a markedly reduced body size was seen in the surviving adults [36]. This reduction in body size was caused by a decrease in cell size rather than a decrease in the actual cell number [36].…”

RNA Interference-Mediated Repression of S6 Kinase 1 Impairs Root Nodule Development in Soybean

“…While it is not known if TOR kinase is involved in controlling cell proliferation in plants as well, let alone how it is being orchestrated, this strong induction of GmTORs and GmS6K1s obtained in our result suggests that function of TOR pathway may be required for soybean root nodules development although no information is available at present on how the cell proliferation during nodulation is connected to cellular signaling such as TOR pathway. S6K1 has been known as a central regulator of cell and body size in animals (Arsham and Neufeld, 2006) and with recent reports of S6K1 being involved in the control of cell size in plants (Henriques et al, 2010;Montagne et al, 1999), it is highly likely that GmS6K1s play a critical role in nodule growth.…”

“…TOR phosphorylates several proteins including S6 Kinase 1 (S6K1) and 4E-BP1, thereby promoting protein synthesis, ribosomal biogenesis and lipogenesis. S6K-deficient mice exhibited a small size phenotype (Pende et al, 2004), similarly to Drosophila deficient in S6K (Montagne et al, 1999), suggesting S6K1 as a regulator of cell size. T-DNA insertional mutants of TOR of Arabidopsis resulted in premature arrest of embryo development (Menand et al, 2002).…”

BCR/ABL, mRNA translation and apoptosis

“…34 Specifically, S6K1 is considered to take part in the control of cell growth by enhancing mRNA translation. 35 Activated S6K1 enhances translation of 5 0 TOP (terminal oligopyrimidine tract) mRNAs, which contain a short polypyrimidine stretch (4-14 nucleotides) immediately adjacent to the 5 0 cap site. 36 Conversely, 4E-BP1 is a negative regulator of translation that upon phosphorylation dissociates from the eucaryotic translation initiation factor 4E (eIF4E), which, in turn, binds the mRNA 5 0 methyl cap structure and contributes, as part of the eIF4F complex, to the unwinding of the mRNA 5 0 -proximal secondary structure which facilitate the interaction with the 40S ribosomal subunit.…”