Positive Feedback Keeps Duration of Mitosis Temporally Insulated from Upstream Cell-Cycle Events

Regulatory gene circuits with positive-feedback loops control stem cell differentiation, but several mechanisms can contribute to positive feedback. Here, we dissect feedback mechanisms through which the transcription factor PU.1 controls lymphoid and myeloid differentiation. Quantitative live-cell imaging revealed that developing B cells decrease PU.1 levels by reducing PU.1 transcription, whereas developing macrophages increase PU.1 levels by lengthening their cell cycles, which causes stable PU.1 accumulation. Exogenous PU.1 expression in progenitors increases endogenous PU.1 levels by inducing cell cycle lengthening, implying positive feedback between a regulatory factor and the cell cycle. Mathematical modeling showed that this cell cycle–coupled feedback architecture effectively stabilizes a slow-dividing differentiated state. These results show that cell cycle duration functions as an integral part of a positive autoregulatory circuit to control cell fate.

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Positive feedback between lncRNA FLVCR1-AS1 and KLF10 may inhibit pancreatic cancer progression via the PTEN/AKT pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02097-0 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Jiewei Lin ◽

Shuyu Zhai ◽

Siyi Zou ◽

Zhiwei Xu ◽

Jun Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Progression ◽

Positive Feedback ◽

Molecular Mechanisms ◽

Tumor Tissues ◽

And Migration

Abstract Background FLVCR1-AS1 is a key regulator of cancer progression. However, the biological functions and underlying molecular mechanisms of pancreatic cancer (PC) remain unknown. Methods FLVCR1-AS1 expression levels in 77 PC tissues and matched non-tumor tissues were analyzed by qRT-PCR. Moreover, the role of FLVCR1-AS1 in PC cell proliferation, cell cycle, and migration was verified via functional in vitro and in vivo experiments. Further, the potential competitive endogenous RNA (ceRNA) network between FLVCR1-AS1 and KLF10, as well as FLVCR1-AS1 transcription levels, were investigated. Results FLVCR1-AS1 expression was low in both PC tissues and PC cell lines, and FLVCR1-AS1 downregulation was associated with a worse prognosis in patients with PC. Functional experiments demonstrated that FLVCR1-AS1 overexpression significantly suppressed PC cell proliferation, cell cycle, and migration both in vitro and in vivo. Mechanistic investigations revealed that FLVCR1-AS1 acts as a ceRNA to sequester miR-513c-5p or miR-514b-5p from the sponging KLF10 mRNA, thereby relieving their suppressive effects on KLF10 expression. Additionally, FLVCR1-AS1 was shown to be a direct transcriptional target of KLF10. Conclusions Our research suggests that FLVCR1-AS1 plays a tumor-suppressive role in PC by inhibiting proliferation, cell cycle, and migration through a positive feedback loop with KLF10, thereby providing a novel therapeutic strategy for PC treatment.

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Systems-Level Dissection of the Cell-Cycle Oscillator: Bypassing Positive Feedback Produces Damped Oscillations

Cell ◽

10.1016/j.cell.2005.06.016 ◽

2005 ◽

Vol 122 (4) ◽

pp. 565-578 ◽

Cited By ~ 243

Author(s):

Joseph R. Pomerening ◽

Sun Young Kim ◽

James E. Ferrell

Keyword(s):

Cell Cycle ◽

Positive Feedback ◽

Damped Oscillations

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Positive feedback of G1 cyclins ensures coherent cell cycle entry

Nature ◽

10.1038/nature07118 ◽

2008 ◽

Vol 454 (7202) ◽

pp. 291-296 ◽

Cited By ~ 234

Author(s):

Jan M. Skotheim ◽

Stefano Di Talia ◽

Eric D. Siggia ◽

Frederick R. Cross

Keyword(s):

Cell Cycle ◽

Positive Feedback ◽

G1 Cyclins ◽

Cell Cycle Entry

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DURATION OF MITOTIC CYCLE IN BRAIN CELLS OF THE MOSQUITO, AEDES DORSALIS

Canadian Journal of Genetics and Cytology ◽

10.1139/g69-080 ◽

1969 ◽

Vol 11 (3) ◽

pp. 673-676 ◽

Cited By ~ 5

Author(s):

Asit B. Mukherjee ◽

Don M. Rees

Keyword(s):

Cell Cycle ◽

High Resolution ◽

Mitotic Cycle ◽

Brain Cells ◽

Duration Of Mitosis ◽

High Resolution Autoradiography

Duration of the mitotic cycle and its various phases in the dividing brain cells of Aedes dorsalis larvae has been determined by high-resolution autoradiography. The length of the cell cycle is 10 hours. The duration of G1 is about 1 hour and 15 minutes, DNA synthetic period (S) is approximately 7 hours, G2 is 1 hour and the duration of mitosis (M) is about 45 minutes.

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Faculty Opinions recommendation of Positive feedback between PU.1 and the cell cycle controls myeloid differentiation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718043605.793485612 ◽

2013 ◽

Author(s):

Ichiro Taniuchi

Keyword(s):

Cell Cycle ◽

Positive Feedback ◽

Myeloid Differentiation

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The duration of mitosis and daughter cell size are modulated by nutrients in budding yeast

The Journal of Cell Biology ◽

10.1083/jcb.201609114 ◽

2017 ◽

Vol 216 (11) ◽

pp. 3463-3470 ◽

Cited By ~ 29

Author(s):

Ricardo M. Leitao ◽

Douglas R. Kellogg

Keyword(s):

Cell Cycle ◽

Cell Size ◽

Daughter Cell ◽

Slow Growth ◽

Budding Yeast ◽

Size Control ◽

G1 Phase ◽

Large Reduction ◽

Duration Of Mitosis ◽

Cell Cycle Entry

The size of nearly all cells is modulated by nutrients. Thus, cells growing in poor nutrients can be nearly half the size of cells in rich nutrients. In budding yeast, cell size is thought to be controlled almost entirely by a mechanism that delays cell cycle entry until sufficient growth has occurred in G1 phase. Here, we show that most growth of a new daughter cell occurs in mitosis. When the rate of growth is slowed by poor nutrients, the duration of mitosis is increased, which suggests that cells compensate for slow growth in mitosis by increasing the duration of growth. The amount of growth required to complete mitosis is reduced in poor nutrients, leading to a large reduction in cell size. Together, these observations suggest that mechanisms that control the extent of growth in mitosis play a major role in cell size control in budding yeast.

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