PMID- 22345078
OWN - NLM
STAT- MEDLINE
DCOM- 20121029
LR  - 20220223
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 113
IP  - 7
DP  - 2012 Jul
TI  - Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of 
      Rac1 pre-mRNA splicing.
PG  - 2319-29
LID - 10.1002/jcb.24103 [doi]
AB  - Rac1b is an alternatively spliced isoform of the small GTPase Rac1 that includes 
      the 57-nucleotide exon 3b. Rac1b was originally identified through its 
      over-expression in breast and colorectal cancer cells, and has subsequently been 
      implicated as a key player in a number of different oncogenic signaling pathways, 
      including tumorigenic transformation of mammary epithelial cells exposed to 
      matrix metalloproteinase-3 (MMP-3). Although many of the cellular consequences of 
      Rac1b activity have been recently described, the molecular mechanism by which 
      MMP-3 treatment leads to Rac1b induction has not been defined. Here we use 
      proteomic methods to identify heterogeneous nuclear ribonucleoprotein (hnRNP) A1 
      as a factor involved in Rac1 splicing regulation. We find that hnRNP A1 binds to 
      Rac1 exon 3b in mouse mammary epithelial cells, repressing its inclusion into 
      mature mRNA. We also find that exposure of cells to MMP-3 leads to release of 
      hnRNP A1 from exon 3b and the consequent generation of Rac1b. Finally, we analyze 
      normal breast tissue and breast cancer biopsies, and identify an inverse 
      correlation between expression of hnRNP A1 and Rac1b, suggesting the existence of 
      this regulatory axis in vivo. These results provide new insights on how 
      extracellular signals regulate alternative splicing, contributing to cellular 
      transformation and development of breast cancer.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Pelisch, Federico
AU  - Pelisch F
AD  - Instituto de Fisiologia, Biologia Molecular y Neurociencias-Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Exactas y Naturales, 
      Universidad de Buenos Aires, Buenos Aires, Argentina.
FAU - Khauv, Davitte
AU  - Khauv D
FAU - Risso, Guillermo
AU  - Risso G
FAU - Stallings-Mann, Melody
AU  - Stallings-Mann M
FAU - Blaustein, Matias
AU  - Blaustein M
FAU - Quadrana, Leandro
AU  - Quadrana L
FAU - Radisky, Derek C
AU  - Radisky DC
FAU - Srebrow, Anabella
AU  - Srebrow A
LA  - eng
GR  - CA116201/CA/NCI NIH HHS/United States
GR  - CA132879/CA/NCI NIH HHS/United States
GR  - P50 CA116201/CA/NCI NIH HHS/United States
GR  - R01 CA132879/CA/NCI NIH HHS/United States
GR  - N02-CO-41101/CO/NCI NIH HHS/United States
GR  - R01 CA122086/CA/NCI NIH HHS/United States
GR  - CA122086/CA/NCI NIH HHS/United States
GR  - N02CO41101/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Heterogeneous Nuclear Ribonucleoprotein A1)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoprotein Group A-B)
RN  - 0 (Neuropeptides)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA Precursors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Rac1 protein, mouse)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - *Alternative Splicing
MH  - Animals
MH  - Cell Line, Tumor
MH  - Epithelial Cells
MH  - Female
MH  - Heterogeneous Nuclear Ribonucleoprotein A1
MH  - Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics/*metabolism
MH  - Mammary Glands, Animal
MH  - Mammary Neoplasms, Animal/genetics/metabolism/pathology
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Mice
MH  - Neuropeptides/*metabolism
MH  - Protein Isoforms/genetics/metabolism
MH  - Proteomics
MH  - RNA Precursors/genetics/metabolism
MH  - RNA Splicing
MH  - RNA, Messenger/metabolism
MH  - rac GTP-Binding Proteins/*metabolism
MH  - rac1 GTP-Binding Protein
PMC - PMC3927408
MID - NIHMS547661
EDAT- 2012/02/22 06:00
MHDA- 2012/10/30 06:00
PMCR- 2014/02/18
CRDT- 2012/02/21 06:00
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/10/30 06:00 [medline]
PHST- 2014/02/18 00:00 [pmc-release]
AID - 10.1002/jcb.24103 [doi]
PST - ppublish
SO  - J Cell Biochem. 2012 Jul;113(7):2319-29. doi: 10.1002/jcb.24103.