Journal
MOLECULAR CELL
Volume 27, Issue 2, Pages 183-196Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2007.05.034
Keywords
-
Categories
Funding
- NCI NIH HHS [R21 CA104429, CA104429] Funding Source: Medline
- NIGMS NIH HHS [R01 GM062281-06, GM062281, R01 GM062281-07, R01 GM062281] Funding Source: Medline
Ask authors/readers for more resources
Cellular senescence is an irreversible proliferation arrest of primary cells and an important tumor suppression process. Senescence is often characterized by domains of facultative heterochromatin, called senescence-associated heterochromatin foci (SAHF), which repress expression of proliferation-promoting genes. Formation of SAHF is driven by a complex of histone chaperones, HIRA and ASF1a, and depends upon prior localization of HIRA to PML nuclear bodies. However, how the SAHF assembly pathway is activated in senescent cells is not known. Here we show that expression of the canonical Wnt2 ligand and downstream canonical Wnt signals are repressed in senescent human cells. Repression of Wnt2 occurs early in senescence and independently of the pRB and p53 tumor suppressor proteins and drives relocalization of HIRA to PML bodies, formation of SAHF and senescence, likely through GSK3 beta-mediated phosphorylation of HIRA. These results have major implications for our understanding of both Wnt signaling and senescence in tissue homeostasis and cancer progression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available