KEAP1: Key Regulator of Cell-Cell Adhesion and Cell Proliferation

Target Name: KEAP1

NCBI ID: G9817

KEAP1: Key Regulator of Cell-Cell Adhesion and Cell Proliferation

KEAP1 (KEAP1 delta C) is a protein that is expressed in many tissues throughout the body. It is a key regulator of cell-cell adhesion, and is involved in the development and maintenance of tissues such as the skin, heart, and brain. In recent years, KEAP1 has gained interest as a potential drug target or biomarker due to its involvement in various diseases, including cancer, neurodegenerative diseases, and autoimmune disorders.

KEAP1 was first identified in the late 1990s as a protein that was expressed in various tissues, including the brain, heart, skin, and lungs. It is a 21-kDa transmembrane protein that consists of an extracellular domain, a transmembrane region, and an intracellular domain. The extracellular domain of KEAP1 contains a N-terminal region that is involved in the formation of a complex with other proteins, including the transcription factor NF-kappa-B. The transmembrane region of KEAP1 contains a variety of different proteins that are involved in the regulation of cell-cell adhesion.

One of the most significant functions of KEAP1 is its role in cell-cell adhesion. KEAP1 helps to regulate the formation of tight junctions, which are specialized structures that mediate the transfer of electrical signals between cells. tight junctions are critical for maintaining the integrity of tissues and are involved in various physiological processes, including sensory perception and ion homeostasis.

In addition to its role in cell-cell adhesion, KEAP1 is also involved in the regulation of cell proliferation. It has been shown to play a role in the G1 phase of the cell cycle, which is responsible for cell growth and preparation for cell division. In addition, KEAP1 has also been shown to promote the G2 phase of the cell cycle and to inhibit the G0 phase.

KEAP1 has also been shown to be involved in the regulation of various signaling pathways. For example, it has been shown to be involved in the regulation of the TGF-β pathway, which is a well-known signaling pathway that is involved in the regulation of cell growth, differentiation, and survival. In addition, KEAP1 has also been shown to be involved in the regulation of the PI3K/AKT signaling pathway, which is involved in the regulation of cell survival and metabolism.

In conclusion, KEAP1 is a protein that is involved in a variety of physiological processes throughout the body. Its role in cell-cell adhesion, cell proliferation, and signaling pathways has made it a potential drug target or biomarker. Further research is needed to fully understand the functions of KEAP1 and its potential as a drug target or biomarker.

Protein Name: Kelch Like ECH Associated Protein 1

Functions: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination (PubMed:14585973, PubMed:15379550, PubMed:15572695, PubMed:15983046, PubMed:15601839). KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (PubMed:19489739, PubMed:16006525, PubMed:17127771, PubMed:18251510, PubMed:29590092). In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2 (PubMed:20452972). The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation (PubMed:28380357). The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome (PubMed:15379550, PubMed:17046835)

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