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Depletion of the Poly(C)-binding Proteins αCP1 and αCP2 from K562 Cells Leads to p53-independent Induction of Cyclin-dependent Kinase Inhibitor (CDKN1A) and G1 Arrest
- Source :
- Journal of Biological Chemistry. 284:9039-9049
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- The alpha-globin poly(C)-binding proteins (alphaCPs) comprise an abundant and widely expressed set of K-homolog domain RNA-binding proteins. alphaCPs regulate the expression of a number of cellular and viral mRNAs at the levels of splicing, stability, and translation. Previous surveys have identified 160 mRNAs that are bound by alphaCP in the human hematopoietic cell line, K562. To explore the functions of these alphaCP/mRNA interactions, we identified mRNAs whose levels are altered in K562 cells acutely depleted of the two major alphaCP proteins, alphaCP1 and alphaCP2. Microarray analysis identified 27 mRNAs that are down-regulated and 14 mRNAs that are up-regulated in the alphaCP1/2-co-depleted cells. This alphaCP1/2 co-depletion was also noted to inhibit cell proliferation and trigger a G(1) cell cycle arrest. Targeted analysis of genes involved in cell cycle control revealed a marked increase in p21(WAF) mRNA and protein. Analysis of mRNP complexes in K562 cells demonstrates in vivo association of p21(WAF) mRNA with alphaCP1 and alphaCP2. In vitro binding assays indicate that a 127-nucleotide region of the 3'-untranslated region of p21(WAF) interacts with both alphaCP1 and alphaCP2, and co-depletion of alphaCP1/2 results in a marked increase in p21(WAF) mRNA half-life. p21(WAF) induction and G(1) arrest in the alphaCP1/2-co-depleted cells occur in the absence of p53 and are not observed in cells depleted of the individual alphaCP isoforms. The apparent redundancy in the actions of alphaCP1 and alphaCP2 upon p21(WAF) expression correlates with a parallel redundancy in their effects on cell cycle control. These data reveal a pivotal role for alphaCP1 and alphaCP2 in a p53-independent pathway of p21(WAF) control and cell cycle progression.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Gene isoform
Molecular Sequence Data
Retinoblastoma Protein
Biochemistry
DNA-binding protein
Heterogeneous-Nuclear Ribonucleoproteins
Cyclin H
Phosphoserine
Cyclin-dependent kinase
Cyclins
Humans
RNA, Messenger
RNA, Small Interfering
3' Untranslated Regions
Molecular Biology
Messenger RNA
Base Sequence
biology
Cell growth
G1 Phase
RNA-Binding Proteins
Translation (biology)
Cell Biology
Molecular biology
Cell biology
DNA-Binding Proteins
RNA: Processing and Catalysis
Gene Expression Regulation
biology.protein
Tumor Suppressor Protein p53
K562 Cells
G1 phase
Protein Binding
K562 cells
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 284
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....0c7b14196e4185705be53aff4d8204ef
- Full Text :
- https://doi.org/10.1074/jbc.m806986200