Inhibition of Proteasome Function Prevents Thymocyte Apoptosis: Involvement of Ornithine Decarboxylase

Grassilli, Emanuela; Benatti, Francesca; Dansi, Paola; Giammarioli, Anna Maria; Malorni, Walter; Franceschi, Claudio; Desiderio, Maria Alfonsina

doi:10.1006/bbrc.1998.9291

Cited by 23 publications

(13 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This effect was attributed to the prevention of ODC degradation [27]. However, since 26S proteasome is not exclusively involved in ODC degradation, but more generally in the degradation of ubiquinated proteins [9], the suggestion of Grassilli et al [27] is only one among several possible interpretations.…”

Section: Polyamines and The Expression Of Growth-related Genesmentioning

confidence: 99%

Polyamines and apoptosis

2005

View full text Add to dashboard Cite

Apoptosis designates genetically-programmed mechanisms of cell death. Damage to DNA or to other vital molecules propagates a cascade of reactions, which activate death programs inside the cell [1]. Physiologically apoptosis is an integral part in embryonic development, and the regulation of organ homeostasis. Apoptotic mechanisms are also exploited for tumour therapy [2]. Polyamines and apoptosis AbstractThe natural polyamines putrescine, spermidine and spermine are in multiple ways involved in cell growth and the maintenance of cell viability. In the course of the last 15 years more and more evidence hinted also at roles in gene regulation. It is therefore not surprising that the polyamines are involved in events inherent to genetically programmed cell death. Following inhibition of ornithine decarboxylase, a key step in polyamine biosynthesis, numerous links have been identified between the polyamines and apoptotic pathways. Examples of activation and prevention of apoptosis due to polyamine depletion are known for several cell lines. Elevation of polyamine concentrations may lead to apoptosis or to malignant transformation. These observations are discussed in the present review, together with possible mechanisms of action of the polyamines. Contradictory results and incomplete information blur the picture and complicate interpretation. Since, however, much interest is focussed at present on all aspects of programmed cell death, a considerable progress in the elucidation of polyamine functions in apoptotic signalling pathways is expected, even though enormous difficulties oppose pinpointing specific interactions of the polyamines with pro-and anti-apoptotic factors. Such situation is quite common in polyamine research.

show abstract

Section: Polyamines and The Expression Of Growth-related Genesmentioning

confidence: 99%

Polyamines and apoptosis

2005

View full text Add to dashboard Cite

show abstract

“…Another concept regarding the role of the proteasome in corticosteroid-induced apoptosis comes from the work of Grassilli et al 30 They found that polyamine levels decrease in thymocytes undergoing apoptosis in response to dexamethasone treatment due to accelerated degradation of ornithine decarboxylase by the proteasome. Inhibition of proteasome function preserves polyamine synthesis in association with inhibition of corticosteroidinduced apoptosis.…”

Section: Multicatalytic Proteasomementioning

confidence: 99%

“…Inhibition of proteasome function preserves polyamine synthesis in association with inhibition of corticosteroidinduced apoptosis. 30 Another target of the proteasome in corticosteroidinduced apoptosis is the cyclin dependent kinase inhibitor, p27Kip1. 31 Following treatment with dexamethasone, the level of p27Kip1 in thymocytes decreases due to proteasome-mediated degradation, a process that is inhibited by Bcl-2 overexpression and accelerated by Bax.…”

Section: Multicatalytic Proteasomementioning

confidence: 99%

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

2002

View full text Add to dashboard Cite

Glucocorticosteroid hormones induce apoptosis in lymphocytes. Therefore, glucocorticoids are commonly used as immunosuppressive and chemotherapeutic agents. This review examines many facets of the process by which glucocorticoids induce apoptosis. This process is divided into three stages, an initiation stage that involves glucocorticoid receptor-mediated gene regulation, a decision stage that involves the counterbalancing influence of prosurvival and proapoptotic factors, and the execution stage which involves caspase and endonuclease activation. Many aspects of glucocorticoid-induced apoptosis, such as mitochondrial dysfunction and caspase activation, are important steps in virtually all forms of apoptosis. But the process glucocorticoid-induced apoptosis differs from other forms of apoptosis in terms of initiation at the transcriptional level and involvement of the multicatalytic proteasome and calcium. Moreover, the abundant opportunity for crosstalk between the glucocorticoid receptor and other signaling pathways increases the complexity of glucocorticoid-induced apoptosis and its regulation.

show abstract

“…c-Fos, NFkB, AP-1 [116,117]), enzymes whose activity is essential for cell proliferation (e.g. ornithine decarboxylase [118]), cell cycle regulatory proteins (e.g. p27 Kip1 [119]), and proteins that normally repress caspases (e.g.…”

Section: Targets Of Proteasome-dependent Degradation During Apoptosismentioning

confidence: 99%

Regulation of apoptosis by the ubiquitin and proteasome pathway

Wójcik

2002

J Cellular Molecular Medi

105

View full text Add to dashboard Cite

Regulated proteolysis plays important roles in cell physiology as well as in pathological conditions. In most of the cases, regulated proteolysis is carried out by the ubiquitin-and proteasome-dependent proteolytic system, which is also in charge of the bulk of cytoplasmic proteolysis. However, apoptosis or the process of programmed cell death is regulated by a different proteolytic system, i.e. by caspases, a family of specialized cysteine proteases. Nevertheless, there is plenty of evidence of a crosstalk between the apoptotic pathways and the ubiquitin and proteasome system, whose function in apoptosis appears to be very complex. Proteasome inhibitors induce apoptosis in multiple cell types, while in other they are relatively harmless or even prevent apoptosis induced by other stimuli. Proteasomes degrade specific proteins during apoptosis, but on the other hand some components of the proteasome system are degraded by caspases. The knowledge about the involvement of the ubiquitin-and proteasome-dependent system in apoptosis is already clinically exploited, since proteasome inhibitors are being tested as experimental drugs in the treatment of cancer and other pathological conditions, where manipulation of apoptosis is desirable.

show abstract

Inhibition of Proteasome Function Prevents Thymocyte Apoptosis: Involvement of Ornithine Decarboxylase

Cited by 23 publications

References 30 publications

Polyamines and apoptosis

Polyamines and apoptosis

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

Regulation of apoptosis by the ubiquitin and proteasome pathway

Contact Info

Product

Resources

About