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Cell Division

, 7:26

First Online: 26 December 2012Received: 06 November 2012Accepted: 15 November 2012

Abstract

Proteasomes are multicatalytic protease complexes in the cell, involved in the non-lysosomal recycling of intra-cellular proteins. Proteasomes play a critical role in regulation of cell division in both normal as well as cancer cells. In cancer cells this homeostatic function is deregulated leading to the hyperactivation of the proteasomes. Proteasome inhibitors PIs are a class of compounds, which either reversibly or irreversibly block the activity of proteasomes and induce cancer cell death. Interference of PIs with the ubiquitin proteasome pathway UPP involved in protein turnover in the cell leads to the accumulation of proteins engaged in cell cycle progression, which ultimately put a halt to cancer cell division and induce apoptosis. Upregulation of many tumor suppressor proteins involved in cell cycle arrest are known to play a role in PI induced cell cycle arrest in a variety of cancer cells. Although many PIs target the proteasomes, not all of them are effective in cancer therapy. Some cancers develop resistance against proteasome inhibition by possibly activating compensatory signaling pathways. However, the details of the activation of these pathways and their contribution to resistance to PI therapy remain obscure. Delineation of these pathways may help in checking resistance against PIs and deducing effective combinational approaches for improved treatment strategies. This review will discuss some of the signaling pathways related to proteasome inhibition and cell division that may help explain the basis of resistance of some cancers to proteasome inhibitors and underline the need for usage of PIs in combination with traditional chemotherapy.

KeywordsProteasome Cell division Proteasome inhibitors Cell cycle Cancer AbbreviationPIProteasome inhibitor

CDKCyclin dependent kinase

CKICyclin dependent kinase inhibitor

UPPUbiquitin proteasome pathway

UPRUnfolded protein response

ER stressEndoplasmic reticulum stress

3-MA3-Methyladenine

NF-ĸBNuclear factor kappa B

SCFSkp 1-Cul 1-F-box protein

APCAnaphase promoting complex

UBE2CUbiquitin-conjugating enzyme E2C

ROSReactive oxygen species.

JNKc-jun-N-terminal kinase

MAPKMitogen activated protein kinase

DDRDNA damage response

HDACiHistone deacetylase inhibitors.

Electronic supplementary materialThe online version of this article doi:10.1186-1747-1028-7-26 contains supplementary material, which is available to authorized users.

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Autor: Namrata Rastogi - Durga Prasad Mishra

Fuente: https://link.springer.com/







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