Milk yield is a direct reflection of the number of milk-producing cells in the udder at any one time. The gradual decline in daily milk yield that occurs in dairy cows over a lactation cycle is due to loss of these cells through cell death. If this process can be prevented, the efficiency of milk production will be improved. This project is based on the idea that stress alters the physical interaction between three pre-existing cellular proteins, causing two of them to move to different locations in the cell where they induce cell death. These proteins are IGFBP-3, a protein that is involved in cell death through unknown mechanisms, and two nuclear receptors Nur77 and retinoic X receptor-alpha (RXR-alpha), which have been shown to move to the mitochondria and induce cell death under certain conditions. The specific objectives will be to determine if IGFBP-3, Nur77 and/or RXRalpha are necessary for cell death in response to stress in milk-producing cells, to determine how these three molecules physically interact in the nucleus during stress, and to determine if specific chemical pathways in the cell are involved in mediating these interactions. The expected result is that under normal conditions, IGFBP-3 will be found in the nucleus in a complex with the nuclear receptors Nur77 and RXRalpha. During stress, these proteins will be modified by chemical signals so that IGFBP-3 will no longer hold Nur77 and RXRalpha in the nucleus, allowing them to move to the mitochondria where they induce cell death. Information gained from these studies will fill critical gaps in our knowledge of how cell death is regulated in milk-producing cells.
|Effective start/end date||9/1/13 → 8/31/15|
- National Institute of Food and Agriculture (National Institute of Food and Agriculture (NIFA))