KLF4

1. 본문

KLF4 (Krüppel-like factor 4) is a zinc finger transcription factor belonging to the larger SP1-like transcription factor family. It's also known as gut-enriched Krüppel-like factor (GKLF) and Epithelial Zinc Finger protein (EZF).

Here's a breakdown of what KLF4 is and its functions:
Structure:

• Zinc Fingers: KLF4 has three C2H2-type zinc fingers at its C-terminus (carboxyl terminus). These zinc fingers allow it to bind to DNA, specifically to GC-rich sequences.
• Nuclear Localization: It has two nuclear localization sequences, which means it is directed to the cell nucleus where it can perform its function as a transcription factor.
• Domains: The N-terminus contains a transactivation domain, which can activate gene transcription. This region also holds a repression domain to suppress transcription.
• Gene Location: In humans, the *KLF4* gene is located on chromosome 9 and contains 5 exons.

• Transcription Factor: KLF4 can act as both an activator and a repressor of gene expression. It binds to the 5'-CACCC-3' core DNA sequence.
• Cellular Processes: It plays a vital roles in various cellular processes like:
• Cell growth
• Proliferation
• Differentiation
• Apoptosis (programmed cell death)
• Somatic cell reprogramming
• Stem Cells: KLF4 is crucial in maintaining embryonic stem cells (ESCs) and preventing their differentiation. KLF4, along with OCT3/4, SOX2, and c-MYC, is one of the four factors that can induce pluripotent stem cells.
• Tissue Specific Roles:
• Intestine: KLF4 is vital for the development and differentiation of intestinal epithelial cells, especially goblet cells.
• Skin: It is needed to establish the skin's permeability barrier.
• Cornea: KLF4 contributes to corneal homeostasis and epithelial barrier function.
• Vascular System: KLF4 plays a part in regulating vascular inflammation and can influence the development of vascular diseases like atherosclerosis.
• Bones and Teeth: Regulates normal skeletal development
• Reproductive Tract: Important for spermatogenesis in males.
• Kidneys: Involved with differentiation of embryonic stem cells.
• White blood cells: It is involved in the mediation of inflammatory responses.
• Tumor Suppressor/Promoter: KLF4 role in cancer is complex and depends on the type of cancer:
• Tumor Suppressor: Often, KLF4 acts as a tumor suppressor, and its expression is reduced in several cancers, including colorectal, gastric, esophageal, lung, prostate, and bladder cancers.
• Tumor Promoter: In some instances, increased KLF4 expression is linked to tumor promotion, such as in oral squamous cell carcinoma and breast ductal carcinoma.