Alternative titles; symbols
HGNC Approved Gene Symbol: POLDIP2
Cytogenetic location: 17q11.2 Genomic coordinates (GRCh38) : 17:28,346,633-28,357,527 (from NCBI)
By yeast 2-hybrid screen of a human placental cDNA library with POLD2 (600815) as bait, Liu et al. (2003) cloned POLDIP2, which they called PDIP38. The deduced 368-amino acid protein contains a C-terminal region with similarity to bacterial APAG proteins and the FBXO3 (609089) protein, including a motif found in NAD- and FAD-binding proteins that are involved in binding to the ADP moiety. POLDIP2 shares 95% amino acid identity with the mouse ortholog. Northern blot analysis detected an approximately 2.0-kb transcript in HeLa and MCF7 cell total RNA.
Xie et al. (2005) localized POLDIP2 to mitochondria by immunohistochemical studies and colocalization with mitochondrial markers. They identified a mitochondrial targeting signal consisting of the first 35 N-terminal amino acids and a cleavage site between residues 50 and 51.
By yeast 2-hybrid screen with rat Ceacam1 (109770) as bait, Klaile et al. (2007) cloned POLDIP2. In contrast to Xie et al. (2005), Klaile et al. (2007) showed that endogenous human and rat POLDIP2 localized to the nucleus, plasma membrane, and cytoplasm. Subcellular fractionation of HeLa and rat epithelial cells detected POLDIP2 primarily in the cytoplasmic fraction with lesser amounts in the nuclear and mitochondrial fractions. Klaile et al. (2007) concluded that POLDIP2 shuttles between cytoplasmic and nuclear compartments with a minor portion entering the mitochondria.
By yeast 2-hybrid, GST pull-down, PCNA (176740) overlay, and coimmunoprecipitation studies, Liu et al. (2003) showed that POLDIP2 bound PCNA and confirmed POLDIP2 interaction with POLD2. POLDIP2 bound the POLD2-POLD1 polymerase delta heterodimer but was not bound directly to the POLD1 (174761) subunit. Using immunoaffinity chromatography, as well as nondenaturing gel electrophoresis, Liu et al. (2003) demonstrated POLDIP2 association with the DNA polymerase delta complex in HeLa and HEK293 cell extracts.
Xie et al. (2005) showed that purified mature POLDIP2 inhibited PCNA-dependent DNA polymerase delta activity by about 50%. GST pull-down assays detected POLDIP2 interaction with human papillomavirus type 16 (HPV16) E7 protein, which is expressed in HPV-associated cancers. Xie et al. (2005) suggested that POLDIP2 may serve as a bridge between HPV16 E7 and DNA polymerase delta.
By binding assays, immunoprecipitation, and surface plasmon resonance analysis, Klaile et al. (2007) demonstrated that rat Poldip2 interacted with both the long and short Ceacam1 isoforms. Confocal microscopy revealed that, in proliferating rat epithelial cells, perturbation of Ceacam1 by antibody clustering induced increased binding of Poldip2 and rapid translocation to the plasma membrane from the cytoplasm. In quiescent rat epithelial cells, the same treatment induced Poldip2 translocation from the cytoplasm to the nucleus. Coimmunoprecipitation studies showed that Poldip2 and Ceacam1 interacted in clustered proliferating cells; however, interaction was not observed in quiescent cells. Serum activation of serum-starved rat epithelial cells induced Poldip2 translocation to the nucleus.
Liu et al. (2003) determined that the POLDIP2 gene contains 11 exons.
The International Radiation Hybrid Mapping Consortium mapped the POLDIP2 gene to chromosome 17 (RH17855).
Klaile, E., Muller, M. M., Kannicht, C., Otto, W., Singer, B. B., Reutter, W., Obrink, B., Lucka, L. The cell adhesion receptor carcinoembryonic antigen-related cell adhesion molecule 1 regulates nucleocytoplasmic trafficking of DNA polymerase delta-interacting protein 38. J. Biol. Chem. 282: 26629-26640, 2007. [PubMed: 17623671] [Full Text: https://doi.org/10.1074/jbc.M701807200]
Liu, L., Rodriguez-Belmonte, E. M., Mazloum, N., Xie, B., Lee, M. Y. W. T. Identification of a novel protein, PDIP38, that interacts with the p50 subunit of DNA polymerase delta and proliferating cell nuclear antigen. J. Biol. Chem. 278: 10041-10047, 2003. [PubMed: 12522211] [Full Text: https://doi.org/10.1074/jbc.M208694200]
Xie, B., Li, H., Wang, Q., Xie, S., Rahmeh, A., Dai, W., Lee, M. Y. W. T. Further characterization of human DNA polymerase delta interacting protein 38. J. Biol. Chem. 280: 22375-22384, 2005. [PubMed: 15811854] [Full Text: https://doi.org/10.1074/jbc.M414597200]