TY - JOUR

T1 - HSPBs

T2 - Small proteins with big implications in human disease

AU - Kampinga, Harm H.

AU - Garrido, Carmen

PY - 2012/10

Y1 - 2012/10

N2 - Although initially somewhat ignored, recent studies have now clearly established that the diverse members of the human family of small HSPs (HSPB1-HSPB10) play crucial roles in a wide range of cell types to maintain the integrity and function of tissues, in particular that of nervous and muscular tissue. The 10 human HSPBs clearly have overlapping and non-overlapping functional characteristics. Their ability to self- and hetero-oligomerise provides the cells with a large array of potentially different, specific functions. Single HSPB members can have a multitude of functions (moonlighting) and act on different "clients", thus affecting a wide range of different processes or structures that can ultimately affect the rate of aging of tissues and entire organisms. This is underscored by the findings that some inherited diseases involve mutations in several HSPB members that cause premature (mostly muscle and neuronal) tissue degeneration. Inversely, cancer cell resistance to different anticancer therapies is associated with elevated expression of several HSPBs. Still, many unanswered questions exist about the precise functioning of HSPBs, their collaboration with other HSPB members as well as their functions within the entire cellular chaperone network. Also, better insight in the regulation of expression of the various members and how their function is modulated post-translationally is needed. Such may be crucially important to develop means to intervene with their function for therapeutic purposes, which would require functional down-regulation in cancer but up-regulation in, for instance, cardiac or degenerative neuro/neuromuscular diseases. This article is part of a Directed Issue entitled: Small HSPs in physiology and pathology. (C) 2012 Elsevier Ltd. All rights reserved.

AB - Although initially somewhat ignored, recent studies have now clearly established that the diverse members of the human family of small HSPs (HSPB1-HSPB10) play crucial roles in a wide range of cell types to maintain the integrity and function of tissues, in particular that of nervous and muscular tissue. The 10 human HSPBs clearly have overlapping and non-overlapping functional characteristics. Their ability to self- and hetero-oligomerise provides the cells with a large array of potentially different, specific functions. Single HSPB members can have a multitude of functions (moonlighting) and act on different "clients", thus affecting a wide range of different processes or structures that can ultimately affect the rate of aging of tissues and entire organisms. This is underscored by the findings that some inherited diseases involve mutations in several HSPB members that cause premature (mostly muscle and neuronal) tissue degeneration. Inversely, cancer cell resistance to different anticancer therapies is associated with elevated expression of several HSPBs. Still, many unanswered questions exist about the precise functioning of HSPBs, their collaboration with other HSPB members as well as their functions within the entire cellular chaperone network. Also, better insight in the regulation of expression of the various members and how their function is modulated post-translationally is needed. Such may be crucially important to develop means to intervene with their function for therapeutic purposes, which would require functional down-regulation in cancer but up-regulation in, for instance, cardiac or degenerative neuro/neuromuscular diseases. This article is part of a Directed Issue entitled: Small HSPs in physiology and pathology. (C) 2012 Elsevier Ltd. All rights reserved.

KW - HSPB

KW - Heat shock protein

KW - Chaperone

KW - Cancer

KW - Neurodegeneration

KW - HEAT-SHOCK PROTEINS

KW - ALPHA-B-CRYSTALLIN

KW - ATRIAL-FIBRILLATION

KW - DROSOPHILA-MELANOGASTER

KW - MOLECULAR CHAPERONES

KW - MISSENSE MUTATION

KW - HSP27 GENE

KW - EXPRESSION

KW - RESISTANCE

KW - CELLS

U2 - 10.1016/j.biocel.2012.06.005

DO - 10.1016/j.biocel.2012.06.005

M3 - Article

VL - 44

SP - 1706

EP - 1710

JO - International journal of biochemistry & cell biology

JF - International journal of biochemistry & cell biology

SN - 1357-2725

IS - 10

ER -