PMID- 24379358
OWN - NLM
STAT- MEDLINE
DCOM- 20140325
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 111
IP  - 2
DP  - 2014 Jan 14
TI  - Induction of amphiregulin by p53 promotes apoptosis via control of microRNA 
      biogenesis in response to DNA damage.
PG  - 717-22
LID - 10.1073/pnas.1313675111 [doi]
AB  - Upon DNA damage, tumor suppressor p53 determines cell fate by repairing DNA 
      lesions to survive or by inducing apoptosis to eliminate damaged cells. The 
      decision is based on its posttranslational modifications. Especially, p53 
      phosphorylation at Ser46 exerts apoptotic cell death. However, little is known 
      about the precise mechanism of p53 phosphorylation on the induction of apoptosis. 
      Here, we show that amphiregulin (AREG) is identified for a direct target of Ser46 
      phosphorylation via the comprehensive expression analyses. Ser46-phosphorylated 
      p53 selectively binds to the promoter region of AREG gene, indicating that the 
      p53 modification changes target genes by altering its binding affinity to the 
      promoter. Although AREG belongs to a family of the epidermal growth factor, it 
      also emerges in the nucleus under DNA damage. To clarify nuclear function of 
      AREG, we analyze AREG-binding proteins by mass spectrometry. AREG interacts with 
      DEAD-box RNA helicase p68 (DDX5). Intriguingly, AREG regulates precursor microRNA 
      processing (i.e., miR-15a) with DDX5 to reduce the expression of antiapoptotic 
      protein Bcl-2. These findings collectively support a mechanism in which the 
      induction of AREG by Ser46-phosphorylated p53 is required for the microRNA 
      biogenesis in the apoptotic response to DNA damage.
FAU - Taira, Naoe
AU  - Taira N
AD  - Department of Biochemistry, The Jikei University School of Medicine, 3-25-8 
      Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.
FAU - Yamaguchi, Tomoko
AU  - Yamaguchi T
FAU - Kimura, Junko
AU  - Kimura J
FAU - Lu, Zheng-Guang
AU  - Lu ZG
FAU - Fukuda, Shinji
AU  - Fukuda S
FAU - Higashiyama, Shigeki
AU  - Higashiyama S
FAU - Ono, Masaya
AU  - Ono M
FAU - Yoshida, Kiyotsugu
AU  - Yoshida K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131230
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.6.1.- (Ddx5 protein, human)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Amphiregulin
MH  - Apoptosis/*physiology
MH  - Cell Line, Tumor
MH  - Chromatin Immunoprecipitation
MH  - DEAD-box RNA Helicases/metabolism
MH  - DNA Damage/*physiology
MH  - EGF Family of Proteins
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation, Neoplastic/genetics/*physiology
MH  - Glycoproteins/*metabolism
MH  - Humans
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - In Situ Nick-End Labeling
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Mass Spectrometry
MH  - MicroRNAs/*biosynthesis
MH  - Microarray Analysis
MH  - Phosphorylation
MH  - Real-Time Polymerase Chain Reaction
MH  - Tumor Suppressor Protein p53/*metabolism
PMC - PMC3896180
OTO - NOTNLM
OT  - Drosha
OT  - miRNA processing
OT  - microarray
COIS- The authors declare no conflict of interest.
EDAT- 2014/01/01 06:00
MHDA- 2014/03/26 06:00
PMCR- 2014/07/14
CRDT- 2014/01/01 06:00
PHST- 2014/01/01 06:00 [entrez]
PHST- 2014/01/01 06:00 [pubmed]
PHST- 2014/03/26 06:00 [medline]
PHST- 2014/07/14 00:00 [pmc-release]
AID - 1313675111 [pii]
AID - 201313675 [pii]
AID - 10.1073/pnas.1313675111 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):717-22. doi: 
      10.1073/pnas.1313675111. Epub 2013 Dec 30.