Increased amounts of reactive oxygen species (ROS) induce apoptosis in mammalian cells. PUMA (P53 up-regulated modulator of apoptosis), a mitochondrial proapoptotic BH3-only protein, induces rapid apoptosis through a Bax- and mitochondria-dependent pathway. However, the molecular basis of PUMA-induced apoptosis is largely not understood. Using a combination of biophysical and biochemical method...

BH3 (Bcl-2 homology domain 3)-only proteins have an important role in the cisplatin resistance of cells. However, the effect of BH3-only proteins on cisplatin-resistant ovarian cancer cells has not been thoroughly elucidated. Our results from the present study indicate that Puma plays a critical role in the apoptosis of chemo-resistant ovarian cancer cells treated with BetA (betulinic acid). Th...

PUMA (p53-upregulated modulator of apoptosis) is a member of the Bcl-2 homology 3 (BH3)-only subfamily of Bcl-2-related proapoptotic proteins that are implicated in numerous apoptotic pathways responding to developmental signals and cellular stress. Puma was originally identified as a target for the tumor suppressor transcription factor p53 and was shown to play the leading role in p53-mediated...

Intestinal epithelial cell (IEC) apoptosis contributes to the development of ulcerative colitis (UC), an inflammatory bowel disease (IBD) that affects the colon and rectum. Therapies that target the inflammatory cytokine TNF have been found to inhibit IEC apoptosis in patients with IBD, although the mechanism of IEC apoptosis remains unclear. We therefore investigated the role of p53-upregulate...

Lumen formation is essential for mammary morphogenesis and requires proliferative suppression and apoptotic clearance of the inner cells within developing acini. Previously, we showed that knockdown of p53 or p73 leads to aberrant mammary acinus formation accompanied with decreased expression of p53 family targets PUMA and p21, suggesting that PUMA, an inducer of apoptosis, and p21, an inducer ...

Head and neck squamous cell carcinoma (HNSCC) ranks the eighth most common cancer worldwide. The patients often present with advanced disease, which responds poorly to chemoradiation therapy. PUMA is a BH3-only Bcl-2 family protein and a p53 target that is required for apoptosis induced by p53 and various chemotherapeutic agents. In this study, we found that PUMA induction by chemotherapeutic a...

Radiation is one of the most effective cancer treatments. However, gastrointestinal (GI) syndrome is a major limiting factor in abdominal and pelvic radiotherapy. The loss of crypt stem cells or villus endothelial cells has been suggested to be responsible for radiation-induced intestinal damage. We report here a critical role of the BH3-only protein p53 upregulated modulator of apoptosis (PUMA...

Disruption of p53/Puma-mediated apoptosis protects against lethality due to DNA damage. Here we demonstrate the unexpected requirement of the pro-apoptotic p53-target gene Puma to mount a successful innate immune response to bacterial sepsis. Puma⁻/⁻ mice rapidly died when challenged with bacteria. While the immune response in Puma⁻/⁻ mice was unchanged in cell migration, phagocytosis and bacte...

OBJECTIVE The cardiotoxicity of doxorubicin limits its clinical use in the treatment of a variety of solid tumors and malignant hematologic disease. Although the mechanism by which it causes cardiac injury is not yet known, apoptosis has been regarded as one of mechanisms underlying the cardiotoxic effects of doxorubicin. In the present study, we investigates the mechanisms of doxorubicin-induc...