JADE - jade family PHD finger | Elisa - Clia - Antibody - Protein

Background

The JADE family, known for containing the PHD (plant homeodomain) finger motif, includes proteins such as JADE1, JADE2, and JADE3. These proteins are implicated in the regulation of chromatin dynamics and transcriptional control. PHD fingers are zinc finger motifs that recognize and bind to specific histone modifications, particularly trimethylated lysine 4 on histone H3 (H3K4me3), which is associated with active transcription. JADE proteins are integral components of histone acetyltransferase (HAT) complexes, which modify chromatin structure to regulate gene expression. They are involved in various biological processes including DNA damage response, cell cycle progression, and differentiation. The aberrant expression or mutations in JADE proteins are linked to several pathological conditions, including cancer, underscoring their significance in cellular homeostasis and disease.

Protein Structure

JADE proteins are characterized by:

• PHD Finger Domains: Typically containing two or more PHD finger motifs, these domains facilitate binding to histone H3K4me3, thereby influencing chromatin structure and gene regulation.
• Nuclear Localization Signals: These signals ensure that JADE proteins are primarily localized in the nucleus, where they can interact with chromatin.
• Association with HAT Complexes: JADE proteins are part of the HBO1 (histone acetyltransferase binding to ORC1) complex, contributing to histone acetylation and chromatin remodeling.

Classification and Subtypes

The JADE family consists of three primary members:

• JADE1 (PHF17): Implicated in the regulation of transcription and DNA damage response.
• JADE2: Plays roles in cell cycle regulation and transcriptional control.
• JADE3: Involved in chromatin remodeling and transcriptional regulation, with specific functions in cellular differentiation processes.

Function and Biological Significance

JADE proteins play critical roles in various cellular processes:

• Transcriptional Regulation: By binding to H3K4me3 and recruiting HAT complexes, JADE proteins facilitate the acetylation of histones, leading to an open chromatin structure and active transcription.
• Chromatin Remodeling: They are essential components of the HBO1 complex, which acetylates histones H3 and H4, promoting chromatin accessibility and gene activation.
• DNA Damage Response: JADE1, in particular, is involved in the cellular response to DNA damage, helping to maintain genomic stability.
• Cell Cycle Control: JADE proteins influence cell cycle progression by regulating the expression of genes critical for cell division.
• Differentiation: They play roles in the differentiation of various cell types by modulating gene expression patterns.

Clinical Issues

Aberrations in JADE proteins are linked to several diseases:

• Cancer: Overexpression or mutations in JADE proteins, particularly JADE1 and JADE2, have been associated with various cancers. Their role in regulating cell cycle and apoptosis makes them crucial in tumorigenesis.
• Developmental Disorders: Dysregulation of JADE proteins can lead to developmental abnormalities due to their roles in cell differentiation and proliferation.
• Neurological Disorders: Given their involvement in chromatin remodeling and gene regulation, mutations or altered expression of JADE proteins may contribute to neurological conditions.

Summary

The JADE family of PHD finger proteins, including JADE1, JADE2, and JADE3, are pivotal in the regulation of chromatin structure and gene expression. Their ability to recognize specific histone modifications and recruit histone acetyltransferase complexes enables them to play key roles in transcriptional regulation, DNA damage response, and cell cycle control. Dysregulation of JADE proteins is implicated in various diseases, particularly cancer, highlighting their importance in cellular homeostasis. Understanding the molecular functions and interactions of JADE proteins provides valuable insights into their roles in health and disease, offering potential targets for therapeutic intervention.