Krüppel-like factor 4 (gut-enriched Krüppel-like factor) inhibits cell proliferation by blocking G1/S progression of

X Chen1, D C Johns, D E Geiman

  • 1Departments of Medicine and Biological Chemistry, and the Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Insights

Krüppel-like factor 4 (KLF4) inhibits cell proliferation by halting the cell cycle at the G(1)/S phase. This study clarifies KLF4

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Krüppel-like factor 4 (KLF4) is a transcription factor linked to growth arrest.
  • Previous research indicates KLF4 inhibits DNA synthesis, but the mechanism remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which KLF4 inhibits cell proliferation.
  • To investigate the role of KLF4 in cell cycle regulation.

Main Methods:

  • Developed an inducible expression system for KLF4 using ponasterone A and ecdysone receptors.
  • Utilized stably transfected colon cancer cell line (RKO) and recombinant adenovirus.
  • Performed flow cytometric analyses to assess cell cycle progression.

Main Results:

  • Inducible KLF4 expression significantly decreased RKO cell proliferation.
  • KLF4 induction caused a cell cycle block at the G(1)/S phase.
  • Similar G(1)/S phase block observed with adenovirus-mediated KLF4 delivery.

Conclusions:

  • KLF4 exerts its inhibitory effect on cell proliferation primarily at the G(1)/S boundary.
  • KLF4 plays a critical role in regulating cell cycle progression.
  • The inducible system provides a tool for studying KLF4 function.

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Cells Coordinate Growth and Proliferation02:36

Cells Coordinate Growth and Proliferation

Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...