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2014 ; 33
(4
): 879-89
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Role of MTA1 in cancer progression and metastasis
#MMPMID25344802
Sen N
; Gui B
; Kumar R
Cancer Metastasis Rev
2014[Dec]; 33
(4
): 879-89
PMID25344802
show ga
The MTA1 protein contributes to the process of cancer progression and metastasis
through multiple genes and protein targets and interacting proteins with roles in
transformation, anchorage-independent growth, invasion, survival, DNA repair,
angiogenesis, hormone independence, metastasis, and therapeutic resistance.
Because the roles and clinical significance of MTA proteins in human cancer are
discussed by other contributors in this issue, this review will focus on our
current understanding of the underlying principles of action behind the
biological effects of MTA1. MTA proteins control a spectrum of cancer-promoting
processes by modulating the expression of target genes and/or the activity of
MTA-interacting proteins. In the case of MTA1, these functions are manifested
through posttranslational modifications of MTA1 in response to upstream signals,
MTA1 interaction with binding proteins, and the expression of target gene
products. Studies delineating the molecular basis of dual functionality of MTA1
reveal that the functions of MTA1-chromatin-modifying complexes in the context of
target gene regulation are dynamic in nature. The nature and targets of
MTA1-chromatin-modifying complexes are also governed by the dynamic plasticity of
the nucleosome landscape as well as kinetics of activation and inactivation of
enzymes responsible for posttranslational modifications on the MTA1 protein.
These broadly applicable functions also explain why MTA1 may be a "hub" gene in
cancer. Because the deregulation of enzymes and their substrates with roles in
MTA1 biology is not necessarily limited to cancer, we speculate that the lessons
from MTA1 as a prototype dual master coregulator will be relevant for other human
diseases. In this context, the concept of the dynamic nature of corepressor
versus coactivator complexes and the MTA1 proteome as a function of time to
signal is likely to be generally applicable to other multiprotein regulatory
complexes in living systems.
|Chromatin Assembly and Disassembly/*genetics/physiology
[MESH]
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