JADE1

Official Full Name

jade family PHD finger 1

Organism

Homo sapiens

GeneID

79960

Background

Enables transcription coactivator activity. Contributes to histone acetyltransferase activity. Involved in several processes, including negative regulation of canonical Wnt signaling pathway; regulation of cell growth; and regulation of nucleobase-containing compound metabolic process. Acts upstream of or within negative regulation of G1/S transition of mitotic cell cycle. Located in several cellular components, including cytosol; microtubule organizing center; and nuclear speck. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

PHF17;

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Detailed Information

Recent Research Progress

JADE1, Gene for Apoptosis and Differentiation in Epithelia 1, is also called jade family PHD finger. JADE1 mRNA gives rise to 2 protein products: a full-length JADE1L and a truncated splice variant, JADE1S. Among JADE family, JADE1 is one of the most studied gene since it is involved in many cellular and biochemical functions.

JADE1 has multiple roles in the cell cycle, apoptosis, gene regulation and cell signaling. For example, some reports have underlined the involvement of JADE1 in cell cycle regulation, the depletion of JADE1 proteins by RNA interference (siRNA) resulted in slower rates of DNA synthesis in cell cycle-synchronized epithelial cell lines and primary fibroblast cell cultures. In fact, it has been shown that JADE1 involved in a puzzling set of alternative activities that are hard to reconcile. The possible explanation is that the two JADE1 isoforms might be involved in spatial-temporal coordination of the DNA synthesis, cytokinesis and perhaps direct transcription regulation of cell cycle factors. Furthermore, some reports show that JADE1 negatively controls cytokinesis, presumably by contributing to cytokinesis delay. Moreover, JADE1 down-regulation caused increased proportion of multi-nuclear cells, which is indicative of premature and failed cytokinesis.

JADE1 is associated with histone acetyltransferase (HAT) activity. Both JADE1L and JADE1S positively regulates HBO1 (human acetylase binding to ORC1) complex HAT activity. In live cell cultures, JADE1 promotes acetylation of nucleosomal histones by HBO1 and dramatically enhanced bulk histone H4 acetylation.

JADE1 and von Hippel–Lindau tumor suppressor (pVHL) can interact and suggested a role in apoptosis and tumor suppression. The pVHL is a protein product of the human VHL gene which is mutated in von Hippel–Lindau hereditary disease and in the majority of sporadic clear cell renal carcinomas. The pVHL is the first protein partner of JADE1S isoform. Although some aspects of pVHL-JADE1 interactions have been characterized, the molecular mechanisms and more importantly physiological role of such interactions remain unclear. One study reported that JADE1S has intrinsic ubiquitin-ligase activity and is capable of binding and ubiquitination of beta-catenin. Based on that study, a model has been proposed that pVHL regulates beta-catenin abundance through JADE1 and that PHD zinc fingers are required for this activity. Additional experimental proof and a follow up study would need to support this possibility.

In a handful of pilot studies, JADE1 expression was examined in colon cancers and renal carcinomas. JADE1 acts as a tumor suppressor in renal cancer. It inhibits cell growth by inducing apoptosis and decreases the abundance of anti-apoptotic Bcl-2. As a novel cell cycle regulator and candidate transcription factor, JADE1 represents an interesting pathway to explore the pathogenesis of epithelial cancers and regenerative disorders. In fact, two of the JADE1 partners and several proteins closely related to JADE1 are mutated in cancers and are tumor suppressors. The potential role for JADE1 in the renewal of embryonic stem cells and embryonal carcinoma cells was suggested in another screening study which used cultured cell models.

References:

Panchenko M V. Structure, function and regulation of jade family PHD finger 1 (JADE1). Gene, 2016, 589(1):1-11.
Andrea H, et al. Histone acetyl transferase (HAT) HBO1 and JADE1 in epithelial cell regeneration.American Journal of Pathology, 2013, 182(1):152-162.
Siriwardana N S, et al. Cell cycle-dependent chromatin shuttling of HBO1-JADE1 histone acetyl transferase (HAT) complex. Cell Cycle, 2014, 13(12):1885-901.

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