DCAF8

Official Full Name

DDB1 and CUL4 associated factor 8

Organism

Homo sapiens

GeneID

50717

Background

This gene encodes a WD repeat-containing protein that interacts with the Cul4-Ddb1 E3 ligase macromolecular complex. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2009]

Synonyms

GAN2; H326; WDR42A;

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Detailed Information

DDB1 and CUL4 Associated Factor 8 (DCAF8), also called WDR42A, is a substrate-recognition receptor for CUL4-DDB1 E3 ubiquitin ligase. DDB1 and CUL4-associated factor 8 (DDB1-CUL4A8) gene plays a crucial role in the body, particularly in the regulation of cell cycle, gene expression, and cell signaling.

Structure And Function of DCAF8

The DDB1-CUL4A8 gene is composed of several exons and encodes a protein of approximately 400-600 amino acids. The protein is a member of the DDB1-CUL4 ubiquitin ligase complex, which is responsible for the ubiquitination and subsequent degradation of target proteins. The specific function of DDB1-CUL4A8 varies depending on the target protein, but overall, it plays a role in regulating cell cycle progression, gene expression, and cell signaling. Histone H3 can be uniquely polyubiquitinated by CRL4 DCAF8 uber ligase, thereby altering the genetic profile of fetal liver during liver maturation.

DCAF8- related Signal Pathway

DCAF8 is a gene that plays a crucial role in various signaling pathways crucial for cell growth, proliferation, and differentiation. As a component of the Cullin-RING E3 ubiquitin ligase (CRL) complex, DCAF8 is involved in the regulation of protein stability and cellular homeostasis. The primary function of DCAF8 is to target specific proteins for ubiquitination and subsequent degradation, which helps regulate signaling pathways involved in tumorigenesis, inflammation, and cell fate determination. DCAF8 interacts with various proteins within the CRL complex and other cellular components to facilitate the ubiquitination of substrate proteins. One of the keys signaling pathways associated with DCAF8 is the Wnt/β-catenin pathway, which plays a significant role in embryonic development, cell proliferation, and tumorigenesis. DCAF8 has been shown to regulate the stability of β-catenin, a key signaling protein in the Wnt pathway. Impairment of DCAF8 function can lead to aberrant activation of the Wnt/β-catenin pathway, contributing to unwanted cellular proliferation and tumor development. Additionally, DCAF8 is involved in the regulation of other critical signaling pathways such as the Notch, Hedgehog, androgen receptor, and estrogen receptor pathways. Alterations in DCAF8 expression or function can lead to misregulation of these pathways, contributing to a variety of cellular disorders, including cancer and inflammation.

DCAF8 And Diseases

Abnormalities in the DDB1-CUL4A8 gene have been associated with various diseases, including cancer, autoimmune diseases, and neurodegenerative diseases. For example, mutations in the DDB1-CUL4A8 gene have been identified in patients with colorectal cancer, leading to the dysregulation of cell cycle control and increased tumorigenesis. Additionally, DDB1-CUL4A8 has been implicated in the pathogenesis of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, likely due to its role in regulating cell signaling pathways. CRL4 DCAF8 regulates the ubiquitination, degradation, and stability of MLF1 and MLF2. It plays a key role in hematopoiesis, leukemia, and various cancers. DCAF8 p.R317C mutation leads to hereditary motor and sensory neuropathies with giant axons and mild cardiomyopathy. Dcaf8 mRNA levels were significantly upregulated in Miwi knockout GC-2 cells, indicating a potential role for Dcaf8 in histone degradation in the middle stages of spermatogenesis.

References:

Zhang, Xiuli et al. "DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis." Frontiers of medicine vol. 15,2 (2021): 302-312. doi:10.1007/s11684-021-0851-8
Peng, Qingyun et al. "The small molecule PSSM0332 disassociates the CRL4ADCAF8 E3 ligase complex to decrease the ubiquitination of NcoR1 and inhibit the inflammatory response in a mouse sepsis-induced myocardial dysfunction model." International journal of biological sciences vol. 16,15 2974-2988. 19 Sep. 2020, doi:10.7150/ijbs.50186

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