BID regulation by p53 contributes to chemosensitivity
Authors: Peiwen Fei
Wafik S El-Deiry
Joanna K Sax
Stanley J Korsmeyer
Eric Bernhard
Maureen E Murphy
Journal: Nature Cell Biology (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p53 protein; tumour suppression; BID; apoptosis; transcription regulation
Affiliations: Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Abstract:  The role of the p53 protein (encoded by TP53) in tumour suppression relies partly on the ability of p53 to regulate the transcription of genes that are important in cell-cycle arrest and in apoptosis. But the apoptotic pathway mediated by p53 is not fully understood. Here we show that BID, a member of the pro-apoptotic Bcl-2 family of proteins, is regulated by p53. BID mRNA is increased in a p53-dependent manner in vitro and in vivo, with strong expression in the splenic red pulp and colonic epithelium of gamma-irradiated mice. Both the human and the mouse BID genomic loci contain p53-binding DNA response elements that bind p53 and mediate p53-dependent transactivation of a reporter gene. In addition, BID-null mouse embryonic fibroblasts are more resistant than are wild-type fibroblasts to the DNA damaging agent adriamycin and the nucleotide analogue 5-fluorouracil, both of which stabilize endogenous p53. Our results indicate that BID is a p53-responsive 'chemosensitivity gene' that may enhance the cell death response to chemotherapy. 

Retracted: No

PubPeer comments:
 Figure 5a. Much more similar than you would expect. https: imgur.com pdPQbGA , 
 Despite the fact that it has been 18 years, I wanted to look into this a bit more. While the first author who was a PhD student in the lab moved on many years ago, I was in this case able to find the original experiment in her lab notebook in an entry dated 1-14-2002 and the original images on the next page in her notebook. There are crop marks on the images from the original experiments, suggesting the sub-panels that were shown in the published manuscript (although what was cropped doesn t actually match what ended up in the - - at 0 Adriamycin. I was also able to find a lab presentation dated 6-27-2002 that shows the image that ended up in the paper that was published in October of 2002. It is clear to me that the result showing the resistance of the - - cells to Adriamycin is there in the original data. ![file] ![file] ![file] , 
 Two images in Figure 2 seem to show overlapping fields of view of the same tissue. Could the authors please check? *** ![file] , 
 I was able to address a prior concern with this paper regarding an experiment in Figure 5. For the new concern, I agree that the two panels in Figure 2 appear to be duplicated which appears to be an error. The experiment was performed many years ago. It is difficult to properly address this due to the passage of time as people have moved on. There is no time or resources to re-perform the in vivo studies to correct the error from over two decades ago. The error does not impact on the conclusions of the paper published in 2002. Wafik El-Deiry 7-1-2022 ,