Simplify p53: just an activator

'Simplify your life.' In research-contrasting such a popular concept-we are challenged by an ever-expanding plethora of observations and accumulation of knowledge. This leads to the development of increasingly complex models trying to explain all aspects of our world that are subject to scientific endeavor. Recently, a well-known object of study from the life sciences, the tumor suppressor p53, has emerged as an example for which diversity of its apparent functions has actually decreased. p53 has long been described to function as a transcription factor. Initially, the cyclin-dependent kinase inhibitor gene CDKN1A (p21 WAF1/CIP1) had been discovered as transcriptionally activated by p53 [1]. Similar to this early observation, many genes were detected to be activated by the tumor suppressor. Often the genes upregulated by p53 serve in blocking the cell cycle or participate in apoptosis induction. In the years following the discovery that p53 acts as a transcriptional activator, it became apparent that p53 is also able to downregulate gene expression [2]. Interestingly, genes repressed by p53 are often involved in control of the cell cycle as well. Following the observation that p53 can serve as an activating as well as a repressing transcription factor, the question arose how a transcription factor could serve as an activator for one group of genes and as a repressor for another. A diverse spectrum of mechanisms was postulated to encompass these opposing functions [3]. Generally, two principal mechanisms were suggested. The first mechanism assumed direct p53 binding to the target gene. Direct binding is also the central part of the mechanism generally accepted when p53 serves as a transcriptional activator [1;3;4]. Proposed mechanisms of repression through direct p53 binding to the target gene include replacement of activating transcription factors, interference with transcriptional activators, utilization of variations from the canonical p53 binding site or recruitment of repressing factors through p53 [3]. The second class of repression mechanisms does not involve direct binding of p53 to its target genes. This mechanistic group includes complex formation of p53 with other transcriptionally active proteins in solution or with the complex-forming partners bound to DNA. Thereby p53 blocks activating transcription factors bound to DNA or keeps them detached from the DNA through complex formation in solution. Another possible mechanism suggests interference of p53 with the basal transcriptional machinery. Furthermore, several indirect mechanisms were described requiring p53-dependent expression of CDKN1A (p21 WAF1/CIP1) or genes of non-coding RNAs [3]. Although some …