Abberant expression of Aurora kinases and inactivation of wild-type p53 by Mdm2 overexpression are frequent molecular events in acute myelogenous leukemia (AML), and preclinical data for inhibition of Aurora kinases or Mdm2 are promising. However, it remains largely unknown if the viability of cells exposed to Aurora kinase inhibitors depends on the p53 status. We investigated the interaction o...

The ability of Salmonella typhimurium to enter intestinal epithelial cells constitutes a crucial step in pathogenesis. Salmonella invasion of the intestinal epithelium requires bacterial type three secretion system. Type three secretion system is a transport device that injects virulence proteins, called effectors, to paralyze or reprogram the eukaryotic cells. Avirulence factor for Salmonella ...

Aberrant expression of Aurora kinases and inactivation of wild-type p53 by Mdm2 overexpression are frequent molecular events in acute myelogenous leukemia (AML), and preclinical data for inhibition of Aurora kinases or Mdm2 are promising. However, it remains largely unknown whether the viability of cells exposed to Aurora kinase inhibitors depends on the p53 status. We investigated the interact...

During spermatogenesis, germ cells initially expand exponentially through mitoses. A majority of these cells are then eliminated through p53-mediated apoptosis to maintain germline homeostasis. However, the activity of p53 must be precisely modulated, especially suppressed in postmitotic spermatogenic cells, to guarantee robustness of spermatogenesis. Currently, how the suppression is achieved ...

Adeno-associated virus (AAV) infection triggers a DNA damage response in the cell. This response is not induced by viral proteins but by virtue of the structure of AAV ssDNA being recognized by the cell as damaged DNA. The consequence of this is the killing of cells lacking p53 activity. We have observed that cells that lack p21 or pRb activity are also sensitive to AAV-induced cell death. We r...

The tumor suppressor p53 pathway, whose alterations are highly associated with all types of human cancers, plays an essential role in preventing tumor development and progression mostly through its downstream target genes. Over the last decade, a growing list of p53 microRNA (miRNA) targets has been identified as additional downstream players of this pathway. Further studies of these miRNAs hav...

The life history of cancer cells encompasses a series of genetic missteps in which normal cells are progressively transformed into tumor cells that invade surrounding tissues and become malignant. Most prominent among the regulators disrupted in cancer cells are two tumor suppressors, the retinoblastoma protein (RB) and the p53 transcription factor. Here, we discuss interconnecting signaling pa...

The PI3K/Akt and mTOR signaling pathways are important for cell survival and growth, and they are highly activated in cancer cells compared with normal cells. Therefore, these signaling pathways are targets for inducing cancer cell death. The dual PI3K/Akt and mTOR inhibitor NVP-BEZ235 completely inhibited both signaling pathways. However, NVP-BEZ235 had no effect on cell death in human renal c...

Transcriptional activation of MYC is a hallmark of many B cell lineage neoplasms. MYC provides a constitutive proliferative signal but can also initiate ARF-dependent activation of p53 and apoptosis. The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of both the MYC and the ARF-p53 signaling pathways, prompting us to determine if it is involved in the pathogenesis of MYC...