title: Role for c-Abl and p73 in the radiation response of male germ cells.
abstract: p53 plays a central role in the induction of apoptosis of spermatogonia in response to ionizing radiation. In p53(-/-) testes, however, spermatogonial apoptosis still can be induced by ionizing radiation, so p53 independent apoptotic pathways must exist in spermatogonia. Here we show that the p53 homologues p63 and p73 are present in the testis and that p73, but not p63, is localized in the cytoplasm of spermatogonia. Unlike p53, neither p63 nor p73 protein levels were found to increase after a dose of 4 Gy of X-rays. Although p73 protein levels did not increase, its interaction with the non-receptor tyrosine kinase c-Abl and its phosphorylation on tyrosine residues did. c-Abl and p73 co-localize in the cytoplasm of spermatogonia and spermatocytes and in the residual bodies. Furthermore, c-Abl protein levels increase after irradiation. p63 was not found to co-localize or interact with c-Abl neither before nor after irradiation. In conclusion, in the testis ionizing radiation elevates cytoplasmic c-Abl that in turn interacts with p73. This may represent an additional, cytoplasmic, apoptotic pathway. Although less efficient than the p53 route, this pathway may cause spermatogonial apoptosis as observed in p53 deficient mice.
authors.affiliation: Department of Cell Biology, UMCU, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. G.Hamer@lab.azu.nl
authors.forename: G
authors.initials: G
authors.lastname: Hamer
authors.forename: I S
authors.initials: IS
authors.lastname: Gademan
authors.forename: H B
authors.initials: HB
authors.lastname: Kal
authors.forename: D G
authors.initials: DG
authors.lastname: de Rooij
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology; D019000:Phosphotyrosine / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism / Q000502:physiology*; D011839:Radiation, Ionizing; D013090:Spermatocytes / Q000378:metabolism / Q000528:radiation effects; D013093:Spermatogonia / Q000378:metabolism / Q000528:radiation effects; D013094:Spermatozoa / Q000378:metabolism / Q000528:radiation effects*; D013737:Testis / Q000378:metabolism; D015534:Trans-Activators; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D014965:X-Rays
chemical_list: C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C000606460:TP73 protein, human; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D019000:Phosphotyrosine; D016315:Proto-Oncogene Proteins c-abl