Integration of Light Signals by the Retinoblastoma Pathway in the Control of S Phase Entry in the Picophytoplanktonic Cell Ostreococcus

Abstract

Although the decision to proceed through cell division depends largely on the metabolic status or the size of the cell, the timing of cell division is often set by internal clocks such as the circadian clock. Light is a major cue for circadian clock entrainment, and for photosynthetic organisms it is also the main source of energy supporting cell growth prior to cell division. Little is known about how light signals are integrated in the control of S phase entry. Here, we present an integrated study of light-dependent regulation of cell division in the marine green alga Ostreococcus. During early G1, the main genes of cell division were transcribed independently of the amount of light, and the timing of S phase did not occur prior to 6 hours after dawn. In contrast S phase commitment and the translation of a G1 A-type cyclin were dependent on the amount of light in a cAMP–dependent manner. CyclinA was shown to interact with the Retinoblastoma (Rb) protein during S phase. Down-regulating Rb bypassed the requirement for CyclinA and cAMP without altering the timing of S phase. Overexpression of CyclinA overrode the cAMP–dependent control of S phase entry and led to early cell division. Therefore, the Rb pathway appears to integrate light signals in the control of S phase entry in Ostreococcus, though differential transcriptional and posttranscriptional regulations of a G1 A-type cyclin. Furthermore, commitment to S phase depends on a cAMP pathway, which regulates the synthesis of CyclinA. We discuss the relative involvements of the metabolic and time/clock signals in the photoperiodic control of cell division.

Translation-independent circadian control of the cell cycle in a unicellular photosynthetic eukaryote

“…8). As shown in green algae 4,[13][14][15] , the DRBR C. merolae cell enters into the S phase even before growing to a certain threshold size (Fig. 6).…”

“…This observation led us to investigate two types of cell cycle regulators, one that accumulates in association with the cell growth and another that is regulated by circadian rhythms. A key regulator of the G1/S transition in eukaryotic cells, including eukaryotic algae 4,[13][14][15] , is the retinoblastoma (RB) tumour suppressor pathway 16 . RB represses the G1/S transition by binding to the E2F-DP heterodimer, which in turn binds certain specific cis elements of S-phase genes.…”

“…One of the biological processes controlled by circadian rhythms is the temporal gating of cell division, a phenomenon that has been observed in a wide variety of eukaryotic lineages from unicellular organisms to mammals 3 . The circadian gating of cell division is especially evident in unicellular algae, in which cells divide at night [3][4][5][6] .…”

“…In the regenerating liver hepatocytes, expression of wee1 (a suppressor of the G2/M transition) is regulated by TTFL so that the G2/M transition is restricted to the morning, when the WEE1 protein level reaches its lowest point 8 . In the case of photosynthetic eukaryotes, a previous transcriptome analysis suggested a model in which the G1/S transition is regulated by the light and time-dependent transcription of G1/S regulators 4 . However, the mechanism of the circadian gating of cell division and the nature of the advantage conferred by such strictly regulated cyclicity in photosynthetic eukaryotes are both still only poorly understood.…”

Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways

“…Some authors said that downregulation of RB leads to the progression of cell cycle. 62 Micropapillary pattern had a basal level of ERCC1, this indicating that DNA repair may occur with NER activation. TTF1 was overexpressed in this pattern and, according with what has been said before, this fact indicates lung cancer progression and development after the terminal respiratory unit.…”