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J Biol Chem. 2013 Dec 20;288(51):36648-61. doi: 10.1074/jbc.M113.486910. Epub 2013 Nov 12.

The p38-interacting protein (p38IP) regulates G2/M progression by promoting α-tubulin acetylation via inhibiting ubiquitination-induced degradation of the acetyltransferase GCN5.

Author information

1
From the Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275 and.

Abstract

p38-interacting protein (p38IP) is a component of the GCN5 histone acetyltransferase-containing coactivator complex (GCN5-SAGA complex). It remains unclear whether p38IP or GCN5-SAGA is involved in cell cycle regulation. Using RNA interference to knock down p38IP, we observed that cells were arrested at the G2/M phase, exhibiting accumulation of cyclins, shrunken spindles, and hypoacetylation of α-tubulin. Further analysis revealed that knockdown of p38IP led to proteasome-dependent degradation of GCN5. GCN5 associated with and acetylated α-tubulin, and recovering GCN5 protein levels in p38IP knockdown cells by ectopic expression of GCN5 efficiently reversed α-tubulin hypoacetylation and G2/M arrest. During the G2/M transition, the association of α-tubulin with GCN5 increased, and the acetylation of α-tubulin reached a peak. Biochemical analyses demonstrated that the interaction between p38IP and GCN5 depended on the p38IP N terminus (1-381 amino acids) and GCN5 histone acetyltransferase domain and bromodomain. The p38IP N terminus could effectively reverse p38IP depletion-induced GCN5 degradation, thus recovering α-tubulin acetylation and G2/M progression. p38IP-mediated suppression of GCN5 ubiquitination most likely occurs via nuclear sequestration of GCN5. Our data indicate that the GCN5-SAGA complex is required for G2/M progression, mainly because p38IP promotes the acetylation of α-tubulin by preventing the degradation of GCN5, in turn facilitating the formation of the mitotic spindle.

KEYWORDS:

Acetylation; Cell Biology; Cell Cycle; Cell Signaling; Gene Silencing; Molecular Cell Biology; Protein Degradation; gcn5; p38IP; α-Tubulin

PMID:
24220028
PMCID:
PMC3868776
DOI:
10.1074/jbc.M113.486910
[Indexed for MEDLINE]
Free PMC Article
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