Abstract
pp32 belongs to a family of leucine-rich acidic nuclear proteins, which play important roles in many cellular processes including regulation of chromatin remodeling, transcription, RNA transport, transformation and apoptosis. pp32 is described as a new tumor suppressor. It is unknown as to how pp32 works in tumor suppression. We found that overexpression of pp32 in human Jurkat T cells inhibits cell growth, and silenced pp32 promotes growth. We first showed that hyperacetylation and hyperphosphorylation of histone H3 are required for T-cell activation. Phosphorylation of histone H3 precedes acetylation during T-cell activation. pp32 specifically binds to histone H3 and blocks its acetylation and phosphorylation. pp32 directly initiates caspase activity and also promotes granzyme A-mediated caspase-independent cell death. Taken together, pp32 plays a repressive role by inhibiting transcription and triggering apoptosis.
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Abbreviations
- aa:
-
amino acid
- ChIP:
-
chromatin immunoprecipitation
- CRE:
-
cAMP-response element
- EGF:
-
epidermal growth factor
- ER:
-
endoplasmic reticulum
- GFP:
-
green fluorescent protein
- Gzm:
-
granzyme
- HAT:
-
histone acetyltransferase
- IE:
-
immediate-early
- IL-2:
-
interleukin 2
- Lys:
-
lysine
- MAPK:
-
mitogen-activated protein kinase
- NAP:
-
nucleosome assembly protein
- PCAF:
-
p300/CBP-associated factor
- PFP:
-
pore-forming protein
- pI:
-
isoelectric point
- PKC:
-
protein kinase C
- PMA:
-
phorbol myristate acetate
- PP2A:
-
protein phosphatase 2A
- RNAi:
-
RNA interference
- Ser:
-
serine
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Acknowledgements
We thank Dr Lieberman for the helpful discussion and for providing some reagents. This work was supported by the National Science Foundation Committee Grant 30470365 (to ZF).
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Fan, Z., Zhang, H. & Zhang, Q. Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity. Cell Death Differ 13, 1485–1494 (2006). https://doi.org/10.1038/sj.cdd.4401825
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DOI: https://doi.org/10.1038/sj.cdd.4401825
