Abstract
To further investigate the role of p53 in apoptosis in vivo and the interaction between p53 and Bcl-2 in the regulation of cellular apoptosis in vivo, we depleted p53 in Bcl-2-null mice. We found that the interaction between p53 and Bcl-2 are tissue dependent. Specifically, loss of p53 in Bcl-2-/- mice inhibits apoptotic induction in spleen and subsequently inhibits the Bcl-2-null-induced spleen atrophy. Furthermore, p53 deficiency overcomes loss of melanocyte stem cell (MSC)-induced apoptosis and subsequently prevents hair graying in Bcl-2- null mice. In addition, p53 deletion partly inhibits apoptosis in hair follicle keratinocytes, leading to the alleviation of hair growth delay in Bcl-2-null mice. However, p53 absence in Bcl-2-null mice cannot restore other defects in Bcl-2-null mice, including retardation of growth, short ears and polycystic kidney disease.
Highlights
The p53 tumor suppressor activates a series of diverse antiproliferative responses to protect cells from different cellular stresses
We deleted the p53 gene in B-cell leukemia lymphoma 2 (Bcl-2)−/− mice to investigate the genetic interaction between p53 and Bcl-2 in vivo
We found the Bcl-2 knockout phenotype was partially alleviated by the deficiency of p53
Summary
The p53 tumor suppressor activates a series of diverse antiproliferative responses to protect cells from different cellular stresses. Bcl-2 deficiency in mice leads to various abnormalities, such as increased embryonic death, lymphocytopenia, hypopigmentation, polycystic kidney disease (PKD), distorted small intestine, abnormal skeletal development, reduced body weight, postnatal growth retardation and shortened life span [12,13,14,15,16,17,18] These results indicate that the Bcl-2 protein has pleiotropic effects on embryonic development and adult homeostasis in various tissues and cells in vivo. Blocking p53-Bcl-2 interaction decreases Granzyme B-induced Bax activation, cytochrome c release, and effector caspase inactivation, resulting in a reduced sensitivity of target cells to both Granzyme B and CTL/NK-mediated cell death [25]. Loss of p53 in Bcl-2−/− mice inhibited apoptosis induction in spleen and hair follicle melanocytes and keratinocytes, but not in kidney
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