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Novel adenosine/uridine‐rich element‐binding proteins recognize interleukin‐3 ARE in leukemia T cells (749.4)
Author(s) -
Martinez Marina,
Gonzalez Jose,
Lopez Armando,
Gonzalez Carlos
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.749.4
Subject(s) - rna binding protein , myelopoiesis , uridine , transcriptional regulation , biology , transcription factor , leukemia , microbiology and biotechnology , chemistry , cancer research , rna , biochemistry , gene , immunology , haematopoiesis , stem cell
Human Interleukin‐3 (hIL‐3) is a cytokine that promotes myelopoiesis, differentiation of macrophages and granulocytes. Aberrant expression of this lymphokine has been associated with several hematological cancers. IL‐3 3’‐UTR harbors Adenosine/Uridine‐Rich Elements (AREs) involved in its post‐transcriptional control. These regulatory sequences are recognized by specific ARE‐Binding Protein (ARE‐BP) complexes. Previous results from our laboratory estimated five ARE‐BP complexes from 34 to 88 kDa binding to the hIL‐3 ARE using UV‐crosslinking assay. Our goal is to identify novel ARE‐BPs that mediate the post‐transcriptional regulation of hIL‐3. To achieve this goal, RNA affinity purification coupled with MS/MS analysis was performed. Also, an immunoblot analysis to confirm the presence of specific proteins was carried out. These results identified ~40 proteins between 12 to 82kD interacting with the hIL‐3 ARE in acute lymphoblastic leukemia cells. MS/MS results in accordance with previous results from our laboratory showed that HuR and p42hnRNP C1/C2 are components of the ARE‐BPs that recognize the hIL‐3 ARE. In addition, our results identified KSRP and SAM68 as novel hIL‐3 ARE‐BPs. Besides, we found that p45AUF‐1 protein interacts with hIL‐3 ARE. Taken together, these data imply that novel ARE‐BP complexes can play an important role in the IL‐3 post‐transcriptional regulation. Ultimately, elucidating the role of these ARE‐BPs in IL‐3 expression can provide new insights about the ARE‐mediated post‐transcriptional regulatory pathway and blood cancer. Grant Funding Source : MBRS‐RISE Program R25GM061838, UPR‐PES Intitutional funding