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ID 21549
file
creator
Asou, Hiroya
subject
RNA
SIGNALING
NDC
Medical sciences
abstract
Previous gene-targeting studies indicated that Bim, a BIB-only death activator, and p27^KIP1, a cydin-dependent kinase inhibitor, regulate total cell number in the body. Cytokines contribute to this process primarily by negatively regulating the steady-state levels of Bim and p27 mRNAs. Here we present a novel mechanism for cytokine-mediated post-transcriptional regulation of Bim and p27 mRNA levels via the activity of Heat shock cognate protein 70 (Hsc70), which enhances the stability of specific mRNAs by binding to AU-rich elements (AREs) in their 3' -untranslated regions. The RNA-binding potential of Hsc70 is regulated by co-chaperones, including Bag-4 (also SODD), CHIP, Hip and Hsp40. Cytokines that down-regulate Bim and p27 operate via Ras-activated signaling pathways, which in turn control the expression or function of these co-chaperones. Thus, exposure of cells to cytokines ultimately leads to the destabilization of Bim and p27 mRNAs and the promotion of cell division and survival. This unanticipated role for a chaperone/co-chaperone complex in the control of mRNA stability appears to be critical for hematopoiesis and leukemogenesis.
journal title
Molecular Cell
volume
Volume 25
issue
Issue 1
start page
99
end page
112
date of issued
2007-01-12
publisher
Elsevier
issn
1097-2765
ncid
publisher doi
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2007 Elsevier Ltd.
relation url
department
Research Institute for Radiation Biology and Medicine