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Review
. 2019 Oct 18;20(20):5168.
doi: 10.3390/ijms20205168.

Emerging Roles of DDB2 in Cancer

Pauline Gilson  1 , Guillaume Drouot  2 , Andréa Witz  3 , Jean-Louis Merlin  4 , Philippe Becuwe  5 , Alexandre Harlé  6
Affiliations
Review

Emerging Roles of DDB2 in Cancer

Pauline Gilson et al. Int J Mol Sci. .

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.

Keywords: DDB2; DNA repair; cancers; invasion; migration; proliferation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the regulation of the gene encoding the DDB2 (Damage-specific DNA-binding protein 2) protein. The proximal promoter of ddb2 gene harbors response elements for the transcription factors NF-1 (Neurofibromin 1) (orange) and Sp1 (Transcription factor Sp1) (green) upstream of the transcription initiation site. The proximal promoter also contains a response element for p53, in association with BRCA1 (Breast cancer type 1 susceptibility protein), or Tap63γ (Tumor protein 63 isoform gamma) (blue) proteins and the E2F (Transcription factor E2F) transcription factor downstream of the transcription initiation site. The binding of these proteins leads to the regulation of ddb2 gene expression.
Figure 2
Figure 2
Roles of the DDB2 (Damage-specific DNA-binding protein 2) protein and its identified partners. AR (Androgen Receptor), ALDH1A1 (Aldehyde dehydrogenase 1 family, member A1), Bcl-2 (B-cell lymphoma 2), c-Flip (Cellular FLICE-like inhibitory protein, EMT (Epithelial–mesenchymal transition), HEKs (Human epidermal keratinocytes), IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), MEFs (Mouse embryonic fibroblasts), MnSOD (Manganese superoxide dismutase), NEDD4L (Neural precursor cell expressed developmentally downregulated gene 4-like), PAQR3 (Progestin and adipoQ receptor family member 3), TGF-β1 (Transforming growth factor beta 1), VEGF (vascular endothelial growth factor), Zeb1 (Zinc finger E-box-binding homeobox 1).
Figure 3
Figure 3
Identified impacts of the DDB2 protein activity in different solid tumors.
See this image and copyright information in PMC

References

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