Translational control of cyclins

The cell cycle is a fundamental and ordered process in which DNA is replicated and homologous chromosomes are segregated and equally distributed to daughter cells. The rate of protein synthesis oscillates during the cell cycle, indicating the importance of translational control for cell cycle progression [1]. Moreover, translational control allows rapid and reversible alterations of protein levels in response to various physiological and pathological conditions [2]. Therefore, it is important for us to have a comprehensive understanding of cell cycle-dependent translation control.Prior to DNA synthesis, the cell cycle phase termed G1 is a period of cell growth and characterized by a high level of both protein synthesis and metabolic rate. During G1, cells also need to ensure their competency to undergo mitosis [3]. After passing through the G1/S checkpoint, cells enter S phase for DNA replication. However, most mammalian cells pause during G1 and enter a quiescent stage termed G0; certain cell types (e.g. neurons and muscle cells) may remain at this stage and undergo differentiation. Global protein synthesis is largely down-regulated in G0, but a subset of mRNAs is specifically translated to ensure cell survival [1]. At G2/M phase, ~60-80% of cap-dependent translation is inhibited whereas alternative mechanisms of translation may be activated for expression of certain mitotic factors [1].Many key regulatory factors are expressed and activated at very specific points during the cell cycle. For example, the activity of cyclin-dependent kinases (Cdks) oscillates throughout the cell cycle and is essentially modulated by associated cyclins. The expression level of cyclins is primarily regulated by transcription of cyclin genes and turnover of cyclin proteins [4,5]. Over the past two decades, however, translation has also emerged as a key point at which the levels of cell cycle regulators are modulated. In this review, we discuss current knowledge on the translational con