Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of apoptosis-associated proteins was evaluated in premalignant and malignant oral epithelial lesions, to test the hypothesis that protein regulation of apoptosis may be altered in the development of oral squamous cell carcinoma. Ninety archived paraffin-embedded specimens from 25 patients (two or more sequential biopsies each) and eight control specimens were evaluated in immunohistochemically stained sections for tumor suppressor protein p53, p53 binding protein mdm-2, and apoptosis regulatory proteins Bcl-2, Bcl-X, Bax, and Bak. The initial histologic diagnosis for 17/25 patients was either focal keratosis, mild dysplasia, or moderate dysplasia; the initial diagnosis for the remaining eight patients ranged from severe dysplasia to moderately differentiated squamous cell carcinoma. Thirty of 90 specimens showed positive p53 expression, nine of which were dysplasias. In patients with one or more lesions displaying p53 expression, there was increased intensity of staining with disease progression. Bak was expressed in 57/90 specimens, including 27 dysplasias of various grades. There was also a significantly increased intensity of Bak staining with disease progression, which did not appear to be dependent upon p53 status. Bcl-X was expressed in 73/90 specimens, with staining displayed earlier in premalignant lesions than either p53 or Bak. Ten of 90 specimens were positive for Bcl-2 (all were dysplasias or carcinomas), and only 2/90 specimens were positive for Bax. Eleven of 90 specimens were positive for mdm-2; six of which were also positive for p53. These data show that apoptosis-associated proteins are altered in variable patterns in both premalignant and malignant oral epithelial lesions. p53 and especially Bak and Bcl-X are expressed early; Bax is largely absent; and Bcl-2 and mdm-2 show sporadic expression in the development of oral premalignant and malignant disease.
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PMID:Apoptosis-associated proteins and the development of oral squamous cell carcinoma. 1021 14

The p53 binding protein 2 (53BP2) has been initially identified as an interacting protein to p53 and subsequent studies have shown that it also interacts with Bcl-2 and NF-kappaB p65 subunit. We have previously found that the TP53BP2 gene encoding 53BP2 protein is a single copy gene and has been mapped to the long arm of chromosome 1 at q42.1. The subsequent studies revealed that TP53BP2 encodes two proteins, 53BP2 and ASPP2, of 1005 and 1128 amino acids, respectively. ASPP2 contains additional 123 amino acids to the N-terminus of 53BP2. In this study, we have examined the genomic organization of TP53BP2 transcripts and found that it encodes two mRNA species, either with (53BP2) or without exon 3 (ASPP2), by alternative splicing in various cell lines and tissues. Thus, we propose to call these proteins as 53BP2S (short) and 53BP2L (long), respectively.
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PMID:Expression of 53BP2 and ASPP2 proteins from TP53BP2 gene by alternative splicing. 1476 26

The p53 binding protein 2 (53BP2) has been identified as the interacting protein to p53, Bcl-2, and p65 subunit of nuclear factor kappaB (NF-kappaB). The TP53BP2 gene encodes two splicing variants, 53BP2S and 53BP2L, previously known as apoptosis stimulating protein 2 of p53 (ASPP2). We found that these 53BP2 proteins are located predominantly in the cytoplasm and induce apoptosis as demonstrated by cleavage of poly ADP ribose polymerase (PARP) and annexin V staining. Furthermore, we demonstrate that 53BP2 is located in the mitochondria and induces apoptosis associated with depression of the mitochondrial trans-membrane potential (DeltaPsim) and activation of caspase-9. From these findings we conclude that 53BP2 induces apoptosis through the mitochondrial death pathway.
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PMID:53BP2 induces apoptosis through the mitochondrial death pathway. 1574 14

The p53 binding protein 2 (53BP2) has been identified independently as the interacting protein to p53, Bcl-2, and p65 subunit of nuclear factor kappaB (NF-kappaB). It was demonstrated that over-expression of 53BP2 (renamed as 53BP2S) induces apoptotic cell death. In this study we explored the effect of NF-kappaB activation elicited by a physiological NF-kappaB inducer, interleukin-1beta (IL-1beta), and anti-apoptotic Bcl-2 family proteins on the 53BP2S-mediated apoptosis. We found that both NF-kappaB activation and Bcl-2 family proteins could prevent the 53BP2S-mediated depression of mitochondrial transmembrane potential, activation of caspase-9, cleavage of poly ADP ribose polymerase (PARP), and cell death. These observations suggested that 53BP2S/Bbp and its directly or indirectly interacting proteins might play crucial roles in the regulation of apoptosis and contribute to carcinogenesis. It is also suggested that 53BP2S/Bbp induces apoptosis through the mitochondrial death pathway presumably by counteracting the actions of anti-apoptotic Bcl-2 family proteins. The regulatory network of the 53BP2S-mediated apoptosis cascade including its interacting proteins is discussed.
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PMID:Inhibition of the 53BP2S-mediated apoptosis by nuclear factor kappaB and Bcl-2 family proteins. 1609 44

Predictive models are being used increasingly in effort to allow physician and patient expectations to be aligned with outcomes that are based on available data. Most predictive models for men who receive external beam radiotherapy for clinically localized prostate cancer are based on Gleason score, clinical tumor classification, and prostate-specific antigen (PSA) levels. More sophisticated models also have been developed that incorporate treatment-related variables, such as the dose of radiation and the use of androgen-deprivation therapy. Most of the predictive models applied to prostate cancer were derived using PSA recurrence rates as the major endpoint, but clinical endpoints have been incorporated increasingly into predictive models. Biomarkers also are increasingly being added to predictive models in an effort to strengthen them. The Radiation Therapy Oncology Group (RTOG) has completed studies on a wide range of markers using tissue from 2 phase 3 trials (RTOG 8610 and 9202). To date, preliminary assessments of p53; DNA ploidy; p16/retinoblastoma 1 protein; Ki-67; mouse double-minute p53 binding protein homolog; Bcl-2/Bcl-2-associated X protein; cytosine, adenine, and guanine repeats; cyclooxygenase-2; signal transducer and activator of transcription 3; cytochrome P450 3A4; and protein kinase A have been completed. Although they are not ready for widespread, routine use, there are reasons to believe that future models will combine these markers with traditional pretreatment and treatment-related variables and will improve our ability to predict outcome and select the optimal treatment. Cancer 2009;115(13 suppl):3112-20. (c) 2009 American Cancer Society.
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PMID:Predictive models in external beam radiotherapy for clinically localized prostate cancer. 1954 39

Malignant spinal tumors have rapid progression and destruct spines or other tissues, leading to metastasis of peripheral organs, causing high difficulty for surgery, recurrence and worse prognosis, thus severely affecting patient life quality and survival period. Apoptosis stimulating protein 2 of p53 (ASSP2) is one member of p53 binding protein family pro-apoptotic member, and can enhance apoptotic activity via modulating p53 pathway. Previous study found critical roles of ASPP2 in occurrence and progression of tumors, whilst the functional role of mechanism of ASPP2 on malignant spinal tumor cells has not been illustrated. Malignant spinal tumor tissue and adjacent tissues were collected for testing ASPP2 mRNA and protein expression in real-time PCR and Western blot. ASPP2 over-expression vector was used to transfect tumor cells, whilst MTT assay was employed for tumor proliferation, followed by p53 expression in Western blot. Caspase 3 activity assay was employed for testing the effect on cell apoptosis. Flow cytometry was employed for tumor cell apoptosis. Real-time PCR tested expressional change of Bcl2 and Bax. ASPP2 mRNA/protein level was significantly depressed in malignant spinal tumor tissues (P<0.05 compared to adjacent tissues). ASPP2-overexpression vector transfection tumor cells increased apoptosis and inhibited proliferation, accompanied with lower Bcl-2, higher Bax, Caspase 3 and p53 (P<0.05 compared to control group). ASPP2 is down-regulated in malignant spinal tumor tissues. ASPP2 can inhibit malignant spinal tumor cell proliferation via mediating p53 expression for cell apoptosis, thus can work as one molecular target for tumor diagnosis and prognostic analysis.
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PMID:Effects of ASPP2 on proliferation and apoptosis of malignant spinal tumor cells. 3196 54