scholarly journals Losses of the tumor suppressor BIN1 in breast carcinoma are frequent and reflect deficits in programmed cell death capacity

2000 ◽  
Vol 85 (3) ◽  
pp. 376-383 ◽  
Keyword(s):  
Cell Death ◽  
Breast Carcinoma ◽  
Tumor Suppressor ◽  
Programmed Cell Death

scholarly journals MicroRNA (miRNA)-to-miRNA Regulation of Programmed Cell Death 4 (PDCD4)

2019 ◽  
Vol 39 (18) ◽  
Author(s):  
Pamela Ajuyah ◽  
Meredith Hill ◽  
Alireza Ahadi ◽  
Jing Lu ◽  
Gyorgy Hutvagner ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Suppressor ◽  
Programmed Cell Death ◽  
Tumor Suppressor Genes ◽  
Untranslated Region ◽  
Inhibitory Concentration ◽  
Mutational Analysis ◽  
Mirna Regulation ◽  
Programmed Cell Death 4 ◽  
The Relationship

ABSTRACT The regulation of tumor suppressor genes by microRNAs (miRNAs) is often demonstrated as a one-miRNA-to-one-target relationship. However, given the large number of miRNA sites within a 3′ untranslated region (UTR), most targets likely undergo miRNA cooperation or combinatorial action. Programmed cell death 4 (PDCD4), an important tumor suppressor, prevents neoplastic events and is commonly downregulated in cancer. This study investigates the relationship between miRNA 21 (miR-21) and miR-499 in regulating PDCD4. This was explored using miRNA overexpression, mutational analysis of the PDCD4 3′ UTR to assess regulation at each miRNA site, and 50% inhibitory concentration (IC50) calculations for combinatorial behavior. We demonstrate that the first miR-499 binding site within PDCD4 is inactive, but the two remaining sites are both required for PDCD4 suppression. Additionally, the binding of miR-21 to PDCD4 influenced miR-499 activity through an increase in its silencing potency and stabilization of its mature form. Furthermore, adjoining miRNA sites more than 35 nucleotides (nt) apart could potentially regulate thousands of 3′ UTRs, similar to that observed between miR-21 and miR-499. The regulation of PDCD4 serves as a unique example of regulatory action by multiple miRNAs. This relationship was predicted to occur on thousands of targets and may represent a wider mode of miRNA regulation.

scholarly journals Role of Promyelocytic Leukemia (Pml) Protein in Tumor Suppression

2001 ◽  
Vol 193 (4) ◽  
pp. 521-530 ◽  
Author(s):  
Eduardo M. Rego ◽  
Zhu-Gang Wang ◽  
Daniela Peruzzi ◽  
Le-Zhen He ◽  
Carlos Cordon-Cardo ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Suppressor ◽  
Programmed Cell Death ◽  
Retinoic Acid Receptor ◽  
Nuclear Body ◽  
Promyelocytic Leukemia ◽  
Cathepsin G ◽  
Putative Tumor Suppressor Gene ◽  
Cancer Pathogenesis

The promyelocytic leukemia (PML) gene encodes a putative tumor suppressor gene involved in the control of apoptosis, which is fused to the retinoic acid receptor α (RARα) gene in the vast majority of acute promyelocytic leukemia (APL) patients as a consequence of chromosomal translocations. The PMLRARα oncoprotein is thought to antagonize the function of PML through its ability to heterodimerize with and delocalize PML from the nuclear body. In APL, this may be facilitated by the reduction to heterozygosity of the normal PML allele. To determine whether PML acts as a tumor suppressor in vivo and what the consequences of deregulated programmed cell death in leukemia and epithelial cancer pathogenesis are, we crossed PML−/− mice with human cathepsin G (hCG)-PMLRARα or mammary tumor virus (MMTV)/neu transgenic mice (TM), models of leukemia and breast cancer, respectively. The progressive reduction of the dose of PML resulted in a dramatic increase in the incidence of leukemia, and in an acceleration of leukemia onset in PMLRARα TM. By contrast, PML inactivation did not affect neu-induced tumorigenesis. In hemopoietic cells from PMLRARα TM, PML inactivation resulted in impaired response to differentiating agents such as RA and vitamin D3 as well as in a marked survival advantage upon proapoptotic stimuli. These results demonstrate that: (a) PML acts in vivo as a tumor suppressor by rendering the cells resistant to proapoptotic and differentiating stimuli; (b) PML haploinsufficiency and the functional impairment of PML by PMLRARα are critical events in APL pathogenesis; and (c) aberrant control of programmed cell death plays a differential role in solid tumor and leukemia pathogenesis.

Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21Waf1/Cip1

2004 ◽  
Vol 287 (6) ◽  
pp. C1541-C1546 ◽  
Author(s):  
R. Göke ◽  
P. Barth ◽  
A. Schmidt ◽  
B. Samans ◽  
B. Lankat-Buttgereit
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Tumor Suppressor ◽  
Programmed Cell Death ◽  
Tumor Cell ◽  
Tumor Progression ◽  
Tumor Cell Lines ◽  
Cyclin Dependent Kinase ◽  
Novel Target ◽  
Cell Death Protein

We show that the recently discovered tumor suppressor pdcd4 represses the transcription of the mitosis-promoting factor cyclin-dependent kinase (CDK)1/cdc2 via upregulation of p21Waf1/Cip1. p21Waf1/Cip1 inhibits CDK4/6 and CDK2. Decrease of CDK4/6 and CDK2 enhances the binding of pRb to E2F/DP, which in turn together bind to and repress the cdc2 promoter. Upregulation of CDK1/cdc2 accompanied by a malignant change was previously reported in colon cancer. We show that expression of pdcd4 as an indirect suppressor of CDK1/cdc2 is lost in progressed carcinomas of lung, breast, colon, and prostate. Furthermore, it seems that localization and expression of pdcd4 directly correlate with tumor progression. Finally, the CDK1/cdc2 inhibitor roscovitine reduces the proliferation of several tumor cell lines, suggesting that inhibition of CDK1/cdc2 may be a useful strategy against malignant transformation. Therefore, pdcd4 might serve as a novel target for antineoplastic therapies.

Abstract 2160: Tumor suppressor p53 down-regulates programmed cell death protein 4 (PDCD4) expression

2021 ◽  
Author(s):  
Wei-Hsiung Yang ◽  
Andrew P. George ◽  
William H. Yang ◽  
Chiung-Min Wang ◽  
Richard H. Yang
Keyword(s):  
Cell Death ◽  
Tumor Suppressor ◽  
Programmed Cell Death ◽  
Tumor Suppressor P53 ◽  
Pdcd4 Expression ◽  
Cell Death Protein

scholarly journals The von Hippel–Lindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2

Oncogene ◽  
2014 ◽  
Vol 34 (6) ◽  
pp. 771-779 ◽  
Author(s):  
P B Essers ◽  
T D Klasson ◽  
T C Pereboom ◽  
D A Mans ◽  
M Nicastro ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Suppressor ◽  
Programmed Cell Death ◽  
Von Hippel Lindau ◽  
Programmed Cell Death 5

Programmed Cell Death Protein 4 (PDCD4) Acts As a Tumor Suppressor in Neuroendocrine Tumor Cells

2004 ◽  
Vol 1014 (1) ◽  
pp. 220-221 ◽  
Author(s):  
RÜDIGER GÖKE ◽  
CORNELIA GREGEL ◽  
ALEXANDRA GÖKE ◽  
RUDOLF ARNOLD ◽  
HARALD SCHMIDT ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Suppressor ◽  
Programmed Cell Death ◽  
Neuroendocrine Tumor ◽  
Tumor Cells ◽  
Cell Death Protein

scholarly journals Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons.

1996 ◽  
Vol 135 (4) ◽  
pp. 1085-1096 ◽  
Author(s):  
R S Slack ◽  
D J Belliveau ◽  
M Rosenberg ◽  
J Atwal ◽  
H Lochmüller ◽  
...  
Keyword(s):  
Cell Death ◽  
Nervous System ◽  
Tumor Suppressor ◽  
Programmed Cell Death ◽  
Recombinant Adenovirus ◽  
Sympathetic Neurons ◽  
Adenovirus Vector ◽  
Wild Type ◽  
Wild Type P53 ◽  
Postmitotic Neurons

Programmed cell death is an ongoing process in both the developing and the mature nervous system. The tumor suppressor gene, p53, can induce apoptosis in a number of different cell types. Recently, the enhanced expression of p53 has been observed during acute neurological disease. To determine whether p53 overexpression could influence neuronal survival, we used a recombinant adenovirus vector carrying wild type p53 to transduce postmitotic neurons. A control consisting of the same adenovirus vector background but carrying the lacZ reporter expression cassette was used to establish working parameters for the effective genetic manipulation of sympathetic neurons. We have found that recombinant adenovirus can be used at titers sufficiently high (10 to 50 multiplicity of infection) to transduce the majority of the neuronal population without perturbing survival, electrophysiological function, or cytoarchitecture. Moreover, we demonstrate that overexpression of wild type p53 is sufficient to induce programmed cell death in neurons. The observation that p53 is capable of inducing apoptosis in postmitotic neurons has major implications for the mechanisms of cell death in the traumatized mature nervous system.

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