POLDIP2 explained

Polymerase delta-interacting protein 2 also known as Polymerase delta-interacting protein of 38 kDa (PDIP38) is encoded by the POLDIP2 gene in humans.^{[1] [2]}

This gene encodes a protein that interacts with the DNA polymerase delta p50 subunit. The encoded protein also interacts with proliferating cell nuclear antigen. Some transcripts of this gene overlap in a tail-to-tail orientation with the gene for tumor necrosis factor, alpha-induced protein 1 (TNFAIP1). POLDIP2 / PDIP38 is a moonlighting protein that has been identified in both the nucleus ^[3] and the mitochondrion ^{[4] [5]}

Interactions

In the nucleus, POLDIP2 has been shown to interact with PCNA, while in the mitochondrion POLDIP2 has been shown to interact with proteins constituting the mitochondrial DNA nucleoid ^[6] and the AAA+ protease CLPXP ^[7] where it modulates both the specificity and stability of this proteolytic machine.

Further reading

• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z . 6 . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells . Genome Research . 10 . 10 . 1546–60 . October 2000 . 11042152 . 310934 . 10.1101/gr.140200 .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . November 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Reports . 1 . 3 . 287–92 . September 2000 . 11256614 . 1083732 . 10.1093/embo-reports/kvd058 .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . 6 . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–44 . October 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Xie B, Li H, Wang Q, Xie S, Rahmeh A, Dai W, Lee MY . Further characterization of human DNA polymerase delta interacting protein 38 . The Journal of Biological Chemistry . 280 . 23 . 22375–84 . June 2005 . 15811854 . 10.1074/jbc.M414597200 . free .
• Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . 6 . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . September 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . free . 8235923 . 11858/00-001M-0000-0010-8592-0 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S . 6 . The LIFEdb database in 2006 . Nucleic Acids Research . 34 . Database issue . D415-8 . January 2006 . 16381901 . 1347501 . 10.1093/nar/gkj139 .
• Klaile E, Müller MM, Kannicht C, Otto W, Singer BB, Reutter W, Obrink B, Lucka L . 6 . The cell adhesion receptor carcinoembryonic antigen-related cell adhesion molecule 1 regulates nucleocytoplasmic trafficking of DNA polymerase delta-interacting protein 38 . The Journal of Biological Chemistry . 282 . 36 . 26629–40 . September 2007 . 17623671 . 10.1074/jbc.M701807200 . free .

Notes and References

1. Liu L, Rodriguez-Belmonte EM, Mazloum N, Xie B, Lee MY . Identification of a novel protein, PDIP38, that interacts with the p50 subunit of DNA polymerase delta and proliferating cell nuclear antigen . The Journal of Biological Chemistry . 278 . 12 . 10041–7 . March 2003 . 12522211 . 10.1074/jbc.M208694200 . free .
2. Web site: Entrez Gene: POLDIP2 polymerase (DNA-directed), delta interacting protein 2.
3. Wong A, Zhang S, Mordue D, Wu JM, Zhang Z, Darzynkiewicz Z, Lee EY, Lee MY . 6 . PDIP38 is translocated to the spliceosomes/nuclear speckles in response to UV-induced DNA damage and is required for UV-induced alternative splicing of MDM2 . Cell Cycle . 12 . 19 . 3184–93 . October 2013 . 23989611 . 3865014 . 10.4161/cc.26221 .
4. Xie B, Li H, Wang Q, Xie S, Rahmeh A, Dai W, Lee MY . Further characterization of human DNA polymerase delta interacting protein 38 . The Journal of Biological Chemistry . 280 . 23 . 22375–84 . June 2005 . 15811854 . 10.1074/jbc.M414597200 . free .
5. Strack PR, Brodie EJ, Zhan H, Schuenemann VJ, Valente LJ, Saiyed T, Lowth BR, Angley LM, Perugini MA, Zeth K, Truscott KN, Dougan DA . 6 . Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA+ protease CLPXP . Communications Biology . 3 . 1 . 646 . November 2020 . 33159171 . 7647994 . 10.1038/s42003-020-01358-6 .
6. Cheng X, Kanki T, Fukuoh A, Ohgaki K, Takeya R, Aoki Y, Hamasaki N, Kang D . 6 . PDIP38 associates with proteins constituting the mitochondrial DNA nucleoid . Journal of Biochemistry . 138 . 6 . 673–8 . December 2005 . 16428295 . 10.1093/jb/mvi169 .
7. Paredes F, Sheldon K, Lassègue B, Williams HC, Faidley EA, Benavides GA, Torres G, Sanhueza-Olivares F, Yeligar SM, Griendling KK, Darley-Usmar V, San Martin A . 6 . Poldip2 is an oxygen-sensitive protein that controls PDH and αKGDH lipoylation and activation to support metabolic adaptation in hypoxia and cancer . Proceedings of the National Academy of Sciences of the United States of America . 115 . 8 . 1789–1794 . February 2018 . 29434038 . 5828627 . 10.1073/pnas.1720693115 . 2018PNAS..115.1789P . free .