title: SPATA18, a spermatogenesis-associated gene, is a novel transcriptional target of p53 and p63.
abstract: The transcription factor p53 functions not only to suppress tumorigenesis but also to maintain normal development and homeostasis. Although p53 was implicated in different aspects of fertility, including spermatogenesis and implantation, the mechanism underlying p53 involvement in spermatogenesis is poorly resolved. In this study we describe the identification of a spermatogenesis-associated gene, SPATA18, as a novel p53 transcriptional target and show that SPATA18 transcription is induced by p53 in a variety of cell types of both human and mouse origin. p53 binds a consensus DNA motif that resides within the first intron of SPATA18. We describe the spatiotemporal expression patterns of SPATA18 in mouse seminiferous tubules and suggest that SPATA18 transcription is regulated in vivo by p53. We also demonstrate the induction of SPATA18 by p63 and suggest that p63 can compensate for the loss of p53 activity in vivo. Our data not only enrich the known collection of p53 targets but may also provide insights on spermatogenesis defects that are associated with p53 deficiency.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Chamutal
authors.initials: C
authors.lastname: Bornstein
authors.forename: Ran
authors.initials: R
authors.lastname: Brosh
authors.forename: Alina
authors.initials: A
authors.lastname: Molchadsky
authors.forename: Shalom
authors.initials: S
authors.lastname: Madar
authors.forename: Ira
authors.initials: I
authors.lastname: Kogan-Sakin
authors.forename: Ido
authors.initials: I
authors.lastname: Goldstein
authors.forename: Deepavali
authors.initials: D
authors.lastname: Chakravarti
authors.forename: Elsa R
authors.initials: ER
authors.lastname: Flores
authors.forename: Naomi
authors.initials: N
authors.lastname: Goldfinger
authors.forename: Rachel
authors.initials: R
authors.lastname: Sarig
authors.forename: Varda
authors.initials: V
authors.lastname: Rotter
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013091:Spermatogenesis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000094323:Sperm Proteins
chemical_list: D024101:Mitochondrial Proteins; D010750:Phosphoproteins; D011506:Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C510989:SPATA18 protein, mouse; D000094323:Sperm Proteins; C495901:TP53 protein, human; C486419:Trp63 protein, mouse