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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.

p63 plays an important role in skin and limb development. This has been clearly demonstrated using mouse models and from studies on human patients harboring p63 mutations. One question that remains unanswered is whether p63 is a tumor suppressor gene or an oncogene. The complexity of the study of p63 is due to the existence of multiple isoforms with opposing functions. The lack of antibodies that distinguish between these isoforms has made the ability to analyze the expression of p63 difficult in human tumors. Many studies have found that p63 is overexpressed in human tumors while other studies have shown a loss of expression of p63. Here, we review the roles of p63 in tumor development and suppression in mouse models and human tumors.

The p53 alterations frequently found in human tumors are missense mutations in the DNA binding domain. These p53 mutations have been shown to have gain-of-function or dominant-negative properties in multiple experiments. The consequences of these p53 mutations at physiological levels on the development of a tumor were unclear. Using mouse models, three recent papers have shed light on the mechanisms of mutant p53 and its family members, p63 and p73, in tumorigenesis. Interestingly, the p53 point mutant mice had a similar phenotype to p53 family compound mutant mice suggesting that there is an interplay between the p53 family members in tumorigenesis and Li-Fraumeni syndrome.