| Description | Prune, a 62 kDa protein, belongs to the DHH family phosphoesterase proteins including RecJ DNA repair exonucleases, pyrophosphatases (PPASEs) and exopolyphospatases (PPX). The DHH super-family can be divided into two main groups on the basis of a C-terminal motif that is very well conserved within each group, but not across the groups. All the members of this super-family possess four other motifs that contain highly conserved charged residues predicted to be responsible for binding ions and catalyzing the phosphoesterase reaction. The most characteristic of these is the third motif, with the signature DHH (Asp-His-His), after which this superfamily was named. Prune is a cyclic nucleotides phosphodiesterase. Due to its protein similarities, Prune might possess other biochemical functionalities within the DHH family of proteins.
The region between amino acids 353-370 of the h-Prune C-terminal is part of the h-Prune DHH2 domain, and in particular constitutes the second part of the last helix and a turned region that interacts with the preceding helix; accordingly, this region in the h-Prune C-terminal has a clear helical propensity. Therefore, the IDP h-Prune C-terminal domain that does not have specific interactions with the globular portions of the whole protein begins at residue 371 and retains the secondary structure propensities (α2 and α3) indicated by the NMR analysis, with a more compact C-terminal region (amino acids 410-440) (Carotenuto et al., 2013). |
| Expression | H-prune overexpression in breast, colorectal and gastric cancers correlates with the degree of lymph-node and distant metastases. |
| Localisation | Prune is localized intracellularly to the cytoplasm. |
| Function | Prune has a role in the metastatic processes through specific inhibition of the anti-metastasis function of nm23-H1 in vivo. Acting as a cytoplasmic cyclic nucleotides phosphodiesterases (cNMP-PDE), Prune is involved in both promoting cellular mobility and stimulating expression of genes involved in metastatic pathways. An additional function has being discovered linking to the first mammalian exopolyphosphatase activity homologue protein, by degrading Poly-P in the cytoplasm, as a source of energy within the cell. |
| Homology | The PRUNE gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, S. cerevisiae, K. lactis, E. gossypii, S. pombe, M. oryzae, and N. crassa. |
| Identification and mapping of human cDNAs homologous to Drosophila mutant genes through EST database searching. |
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| PMID 8640222 |
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| Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction. |
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| Sci Rep. 2013;3:1351. doi: 10.1038/srep01351. |
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| Unraveling genes and pathways influenced by H-prune PDE overexpression: a model to study cellular motility. |
| D'Angelo A, Zollo M. |
| Cell Cycle. 2004 Jun;3(6):758-61. Epub 2004 Jun 14. (REVIEW) |
| PMID 15254413 |
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| The Nm23-H1-h-Prune complex in cellular physiology: a 'tip of the iceberg' protein network perspective. |
| Galasso A, Zollo M. |
| Mol Cell Biochem. 2009 Sep;329(1-2):149-59. doi: 10.1007/s11010-009-0115-4. Epub 2009 Apr 24. (REVIEW) |
| PMID 19390954 |
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| Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility. |
| Garzia L, D'Angelo A, Amoresano A, Knauer SK, Cirulli C, Campanella C, Stauber RH, Steegborn C, Iolascon A, Zollo M. |
| Oncogene. 2008 Mar 20;27(13):1853-64. Epub 2007 Oct 1. |
| PMID 17906697 |
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| Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions. |
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| Mol Cell Biol. 2006 Feb;26(3):898-911. |
| PMID 16428445 |
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| Evidence for interaction between human PRUNE and nm23-H1 NDPKinase. |
| Reymond A, Volorio S, Merla G, Al-Maghtheh M, Zuffardi O, Bulfone A, Ballabio A, Zollo M. |
| Oncogene. 1999 Dec 2;18(51):7244-52. |
| PMID 10602478 |
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| Human metastasis regulator protein H-prune is a short-chain exopolyphosphatase. |
| Tammenkoski M, Koivula K, Cusanelli E, Zollo M, Steegborn C, Baykov AA, Lahti R. |
| Biochemistry. 2008 Sep 9;47(36):9707-13. doi: 10.1021/bi8010847. Epub 2008 Aug 14. |
| PMID 18700747 |
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| Novel pyrimidopyrimidine derivatives for inhibition of cellular proliferation and motility induced by h-prune in breast cancer. |
| Virgilio A, Spano D, Esposito V, Di Dato V, Citarella G, Marino N, Maffia V, De Martino D, De Antonellis P, Galeone A, Zollo M. |
| Eur J Med Chem. 2012 Nov;57:41-50. doi: 10.1016/j.ejmech.2012.08.020. Epub 2012 Aug 23. |
| PMID 23059542 |
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| Overexpression of h-prune in breast cancer is correlated with advanced disease status. |
| Zollo M, Andre A, Cossu A, Sini MC, D'Angelo A, Marino N, Budroni M, Tanda F, Arrigoni G, Palmieri G. |
| Clin Cancer Res. 2005 Jan 1;11(1):199-205. |
| PMID 15671547 |
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