Abstract
Damage-specific DNA-binding protein 2 (DDB2) was originally identified as a DNA damage recognition factor that facilitates global genomic nucleotide excision repair (GG-NER) in human cells. DDB2 also contributes to other essential biological processes such as chromatin remodeling, gene transcription, cell cycle regulation, and protein decay. Recently, the potential of DDB2 in the development and progression of various cancers has been described. DDB2 activity occurs at several stages of carcinogenesis including cancer cell proliferation, survival, epithelial to mesenchymal transition, migration and invasion, angiogenesis, and cancer stem cell formation. In this review, we focus on the current state of scientific knowledge regarding DDB2 biological effects in tumor development and the underlying molecular mechanisms. We also provide insights into the clinical consequences of DDB2 activity in cancers.
Highlights
Damage-specific DNA-binding protein 2 (DDB2) is a 48-kDa protein exclusively localized in the nucleus of mammalian cells
As a recognized member of the DDB1 and CUL4-associated factors (DCAF), DDB2 is in a close contact with the E3 ubiquitin ligase of the Cul4A protein and participates in the degradation of various proteins such as the cyclin-dependent kinase (CDK) inhibitor p27, a well-known negative regulator of the cell cycle [17]
High levels of DDB2 protein and mRNA are reported in ER (Estrogen receptor)-positive and non-invasive breast cancer models compared to ER-negative aggressive breast cancer cells and mammary non-malignant cells [16]
Summary
DDB2 (damage-specific DNA-binding protein 2, known as p48 subunit) is a 48-kDa protein exclusively localized in the nucleus of mammalian cells. Structural analysis of the ddb promoter shows multiple Sp1 (Transcription factor Sp1) -specific binding sites as usually found in gene promoters with a G–C rich sequence lacking a TATA box and suggesting a critical role for Sp1 for the basal expression of DDB2 [5] (Figure 1). DDB2 stimulates the transcriptional activity of the transcription factor E2F1 and the expression of multiple target genes involved in cell cycle progression [3]. As a recognized member of the DDB1 and CUL4-associated factors (DCAF), DDB2 is in a close contact with the E3 ubiquitin ligase of the Cul4A protein and participates in the degradation of various proteins such as the cyclin-dependent kinase (CDK) inhibitor p27, a well-known negative regulator of the cell cycle [17]. We provide insights into the clinical consequences of DDB2 activity in cancers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
