DCAF4

Official Full Name

DDB1 and CUL4 associated factor 4

Organism

Homo sapiens

GeneID

26094

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

WDR21; WDR21A;

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Detailed Information

DDB1 and CUL4 associated factor 4 (DCAF4), also known as CUL4-DDB1-associated protein 4, is a highly conserved protein that belongs to the WD40 repeat protein family. It has been implicated in various cellular processes, including DNA repair, cell cycle regulation, transcription, and ubiquitin-proteasome system (UPS) function. DCAF4 interacts with multiple proteins, such as DDB1, CUL4A/CUL4B, and RAD51, to regulate these processes.

Structure of DCAF4

DCAF4 is a gene that plays a crucial role in the cell cycle, particularly in the G2/M phase transition. The structure of DCAF4 consists of several key domains, including a N-terminal ubiquitin-like (UBL) domain, a central coiled-coil (CC1) domain, and a C-terminal WD-repeat (WD40) domain. These domains enable DCAF4 to interact with various proteins, promoting cell cycle progression and ensuring accurate chromosome segregation during mitosis.

Function And Mechanism of Action

One of the key roles of DCAF4 is in DNA repair, where it interacts with the DNA repair protein RAD51 and promotes its localization to the sites of DNA damage. This interaction is crucial for the repair of double-strand breaks (DSBs) and maintaining genome stability. In addition, DCAF4 has been shown to regulate the cell cycle by interacting with the cell cycle protein CDK4/6 and promoting its ubiquitination and degradation. This interaction is important for cell cycle progression and cell proliferation. DCAF4 also plays a role in transcription regulation by interacting with the transcription factor TFIIH, which is essential for RNA polymerase II-directed transcription. Moreover, DCAF4 has been shown to interact with the ubiquitin ligase complex, CUL4A/CUL4B, and regulate the ubiquitination and degradation of target proteins. This function is important for the maintenance of cellular homeostasis and the removal of damaged or unnecessary proteins.

DCAF4 and Cancer

DCAF4 is a gene that has been implicated in the development and progression of cancer. As a tumor suppressor gene, DCAF4 plays a crucial role in maintaining cellular homeostasis and preventing the uncontrolled growth of cells that can lead to cancer. The primary function of DCAF4 is in DNA repair, where it helps identify and repair damage caused by environmental factors, oxidative stress, and normal cellular processes. Mutations or alterations in the DCAF4 gene can lead to defects in DNA repair, allowing the accumulation of mutations that promote cancer development. DCAF4 interacts with several proteins involved in DNA repair and cell cycle regulation, including DNA polymerase delta (Polδ) and DNA ligase IV (Lig4). These interactions enable the rapid and accurate repair of damaged DNA, maintaining genetic stability and preventing the proliferation of cancer cells. DCAF4 also plays a role in cell invasion and metastasis, which are critical processes in the progression of cancer.

References:

Cui, Haoran et al. "DTL promotes cancer progression by PDCD4 ubiquitin-dependent degradation." Journal of experimental & clinical cancer research: CR vol. 38,1 350. 13 Aug. 2019, doi:10.1186/s13046-019-1358-x
Raisch, Jennifer et al. "Pulse-SILAC and Interactomics Reveal Distinct DDB1-CUL4-Associated Factors, Cellular Functions, and Protein Substrates." Molecular & cellular proteomics: MCP vol. 22,10 (2023): 100644. doi:10.1016/j.mcpro.2023.100644
Yang, Chunmei et al. "Small molecule NSC1892 targets the CUL4A/4B-DDB1 interactions and causes impairment of CRL4DCAF4 E3 ligases to inhibit colorectal cancer cell growth." International journal of biological sciences vol. 16,6 1059-1070. 4 Feb. 2020, doi:10.7150/ijbs.40235

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