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Nikolaev_guide_answers - Guide for Nikolaev et al(2003 Parc...

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Guide for Nikolaev et al. (2003) Parc: A cytoplasmic anchor for p53. Cell 112:29-40. . These questions are intended to help you read the paper in an inquisitive fashion and to help you focus on some of the issues you should understand. Please cover each of these questions during your reading and studying. Please submit the answers to 5 of these questions for your homework assignment. 1. p53 is a transcription factor that is maintained in a latent form in most cells and is activated in response to certain stresses. Name one downstream transcriptional target of p53 that you have already learned about. What is the role of this target protein? p21 is the target. p21 binds to and inhibits the G1-S cyclin-cdk complexes to “brake” the cell cycle during times of DNA damage or other stress. 2. p53 is a transcription factor with a nuclear localization signal that obviously functions in the nucleus. Why are the authors looking for cytoplasmic proteins that might bind to p53? In other words, what is the primary hypothesis of this paper? p53 is degraded and/or sequestered in the cytoplasm during normal cell growth conditions. Only upon DNA damage or other stress does p53 translocate to the nucleus to perform its function (delay the cell cycle long enough for repair or induce cell death in a the event of extensive damage). Mdm2 is known to induce degradation of p53 but what proteins may be acting to hold p53 in the cytoplasm? The hypothesis of this paper is that there are cytoplasmic proteins that sequester p53 in the cytoplasm under normal conditions. Cytoplasmic localization of p53 is correlated with certain cancers.
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