Controlling protein compartmentalization to overcome disease

被引:48
作者
Davis, James R. [1 ]
Kakar, Mudit [1 ]
Lim, Carol S. [1 ]
机构
[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84108 USA
基金
美国国家卫生研究院;
关键词
bi-directional protein switch; mislocalization of proteins; nucleocytoplasmic shuttling; signal sequences; targeting protein compartmentalization for therapy;
D O I
10.1007/s11095-006-9133-z
中图分类号
O6 [化学];
学科分类号
0703 [化学];
摘要
Over the past decade, considerable progress has been made to improve our understanding of the intracellular transport of proteins. Mechanisms of nuclear import and export involving classical receptors have been studied. Signal sequences required for directing a protein molecule to a specific cellular compartment have been defined. Knowledge of subcellular trafficking of proteins has also increased our understanding of diseases caused due to mislocalization of proteins. A specific protein on deviating from its native cellular compartment may result in disease due to loss of its normal functioning and aberrant activity in the "wrong" compartment. Mislocalization of proteins results in diseases that range from metabolic disorders to cancer. In this review we discuss some of the diseases caused due to mislocalization. We further focus on application of nucleocytoplasmic transport to drug delivery. Various rationales to treat diseases by exploiting intracellular transport machinery have been proposed. Although the pathways for intracellular movement of proteins have been defined, these have not been adequately utilized for management of diseases involving mislocalized proteins. This review stresses the need for designing drug delivery systems utilizing these mechanisms as this area is least exploited but offers great potential.
引用
收藏
页码:17 / 27
页数:11
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