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1

A role of NF-B and the proteasome in autoimmunity

100%

Hayashi T., Faustman D.

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vol. 48

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issue 5

353-365

EN

Type 1 diabetes (also known as insulin-dependent diabetes mellitus or juvenile-onset diabetes) is usually caused by T cell-mediated autoimmunity, with a prediabetic state characterized by the production of autoantibodies specific for proteins expressed by pancreatic beta cells. The non-obese diabetic (NOD) mouse is a spontaneous model of type 1 diabetes with a strong genetic component that maps to the major histocompatibility complex (MHC) region of the genome. A specific proteasome defect has been identified in NOD mouse lymphocytes that results from down-regulation of expression of the proteasome subunit LMP2, which is encoded by a gene in the MHC genomic region. This defect both prevents the proteolytic processing required for the production and activation of the transcription factor nuclear facktor-kappaB (NF-kappaB), which plays important roles in immune and inflammatory responses, as well as increases the susceptibility of the affected cells to apoptosis induced by tumor necrosis factor alpha (TNF-alpha). The proteasome dysfunction is both tissue and developmental stage specific and likely contributes to disease pathogenesis and tissue targeting.

2

Anti-tumor chemotherapy utilizing peptide-based approaches ? apoptotic pathways, kinases, and proteasome as targets

88%

Mendoza F. J., Espino P. S., Cann K. L., Bristow N., Mc_Crea K., Los M.

Archivum Immunologiae et Therapiae Experimentalis

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2005

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vol. 53

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issue 1

47-60

EN

The pharmacological sciences are taking advantage of recent discoveries that have defined the molecular pathways governing apoptosis. These signaling cascades are frequently inactivated or distorted by mutations in cancer cells. Peptides derived from critical interaction, phosphorylation, or cleavage sites are the preferred leads (starting points) for the development of new drugs. In this review we summarize recent peptide-based approaches that target MDM2, p53, NF-?B, ErbB2, MAPK, as well as Smac/DIABLO, IAP BIR domains, and Bcl-2 interaction domains, with a specific focus on the BH3 domain. Separate parts of the review deal with proteasome inhibitors, integrin-derived peptides, and molecules that are being tested for tumor-selective delivery of anticancer drugs ('magic bullet' approach). The proteasome inhibitors and integrin-derived peptides show a variety of effects, targeting not only tumor growth, but also angiogenesis, metastasizing potential, and other cancer cell functions. The last part of this review describes approaches that use specific properties (surface receptors, increased enzymatic activities) of cancer cells in order to target them specifically. These new generations of anticancer drugs provide the foundations for therapies with fewer side effects and higher efficacy.

3

Ribophagy ? the novel degradation system of the ribosome

75%

Bakowska-Zywicka K., Tyczewska A.

Biotechnologia

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2009

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issue 1

99-103

EN

Recently biochemists have discovered a new pathway by which the cell selectively degrades ribosomes. The pathway is called ribophagy. Two proteins were identified as crucial for the selective degradation of ribosomes by autophagy: ubiquitin-specific protease 3 (Ubp3) and Ubp3-associated cofactor, Bre5. This fact strengthens the connections between the autophagy and proteasome pathways of protein degradations.

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2 Archivum Immunologiae et Therapiae Experimentalis

1 Biotechnologia

1 2009

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1 Bakowska-Zywicka K.

1 Bristow N.

1 Cann K. L.

1 Espino P. S.

1 Faustman D.

1 Hayashi T.

1 Los M.

1 Mc_Crea K.

1 Mendoza F. J.

1 Tyczewska A.

A role of NF-B and the proteasome in autoimmunity

Anti-tumor chemotherapy utilizing peptide-based approaches ? apoptotic pathways, kinases, and proteasome as targets

Ribophagy ? the novel degradation system of the ribosome