The regulation of the endosomal compartment by p53 the tumor suppressor gene.
The endosomal compartment of the cell is involved in a number of functions including: (a) internalizing membrane proteins to multivesicular bodies and lysosomes; (b) producing vesicles that are secreted from the cell (exosomes); and (c) generating autophagic vesicles that, especially in times of nutrient deprivation, supply cytoplasmic components to the lysosome for degradation and recycling of nutrients. The p53 protein responds to various stress signals by initiating a transcriptional program that restores cellular homeostasis and prevents the accumulation of errors in a cell. As part of this process, p53 regulates the transcription of a set of genes encoding proteins that populate the endosomal compartment and impact upon each of these endosomal functions. Here, we demonstrate that p53 regulates transcription of the genes TSAP6 and CHMP4C, which enhance exosome production, and CAV1 and CHMP4C, which produce a more rapid endosomal clearance of the epidermal growth factor receptor from the plasma membrane. Each of these p53-regulated endosomal functions results in the slowing of cell growth and division, the utilization of catabolic resources and cell-to-cell communication by exosomes after a stress signal is detected by the p53 protein. These processes avoid errors during stress and restore homeostasis once the stress is resolved.
Yu
Xin
X
The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA.
Riley
Todd
T
Levine
Arnold J
AJ
D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
D015513:Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D033921:Vesicular Transport Proteins; D066246:ErbB Receptors