KLF4

2WBS, 2WBU, 4M9E931416600ENSG00000136826ENSMUSG00000003032O43474Q60793NM_001314052NM_004235NM_010637NP_001300981NP_004226NP_034767Kruppel-like factor 4 (KLF4; gut-enriched Krüppel-like factor or GKLF) is a zinc-finger transcription factor, and it was first identified in 1996. KLF4 is a member of the KLF family of transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including Colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs). Kruppel-like factor 4 (KLF4; gut-enriched Krüppel-like factor or GKLF) is a zinc-finger transcription factor, and it was first identified in 1996. KLF4 is a member of the KLF family of transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including Colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs). In humans, the protein is 513 amino acids with a predicted molecular weight of approximately 55kDa and is encoded by the KLF4 gene. The KLF4 gene is conserved in chimpanzee, rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog. KLF4 can activate transcription by interacting via it N-terminus with specific transcriptional co-activators, such as p300-CBP coactivator family. Transcriptional repression by KLF4 is carried out by KLF4 competing with an activator for binding to a target DNA sequence (9-12). KLF4 has been shown to interact with CREB-binding protein. It was found that the transcription factor Klf4 present at the promoter of an enzymatic subunit of telomerase (TERT), where it formed a complex with β-catenin. Klf4 was required for accumulation of β-catenin at the Tert promoter but was unable to stimulate Tert expression in the absence of β-catenin. KLF4 has diverse functions, and has been garnering attention in recent years because some of its functions are apparently contradicting, but mainly since the discovery of its integral role as one of four key factors that are essential for inducing pluripotent stem cells. KLF4 is highly expressed in non-dividing cells and its overexpression induces cell cycle arrest. KLF4 is particularly important in preventing cell division when the DNA is damaged. KLF4 is also important in regulating centrosome number and chromosome number (genetic stability), and in promoting cell survival. However, some studies have revealed that under certain conditions KLF4 may switch its role from pro-cell survival to pro-cell death. KLF4 is expressed in the cells that are non-dividing and are terminally differentiated in the intestinal epithelium, where KLF4 is important in the regulation of intestinal epithelium homeostasis (terminal cell differentiation and proper localization of the different intestinal epithelium cell types). In the intestinal epithelium, KLF4 is an important regulator of Wnt signaling pathway genes of genes regulating differentiation. KLF4 is expressed in a variety of tissues and organs such as: the cornea where it is required for epithelial barrier function and is a regulator of genes required for corneal homeostasis; the skin where it is required for the development of skin permeability barrier function; the bone and teeth tissues where it regulates normal skeletal development; epithelial cell of the mouse male and female reproductive tract where in the males it is important for proper spermatogenesis; vascular endothelial cells where it is critical in preventing vascular leakage in response to inflammatory stimuli; white blood cells where it mediates inflammatory responses cellular differentiation and proliferation; the kidneys where it is involved in the differentiation of embryonic stem cells and induced pluripotent stem (iPS) cells to renal lineage in vitro and its dysregulation has been linked to some renal pathologies.