IRES-mediated translational control of AMAP1 expression during differentiation of monocyte U937 cells.
Global control of mRNA translation plays key roles in cell regulation, including growth, differentiation and apoptosis. Human monocyte-like U937 cells differentiate into macrophage-like cells upon 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, a process which is known to be accompanied with a large decrease in general protein synthesis. Here, we found that protein levels of AMAP1 (also called ASAP1 or DDEF1), a GTPase-activating protein for Arf GTPases, increase several fold during U937 cell differentiation. This increase was not accompanied with a notable increase in the AMAP1 gene transcript, nor seemed to be due to 5'-Cap-dependent mRNA translational activities in differentiated U937 cells. We identified the 5'-untranslated region (5'-UTR) of AMAP1 mRNA, and found that this 5'-UTR exhibits significant internal ribosome entry site (IRES)-dependent translational activity in differentiated U937 cells, but not in undifferentiated cells. Our results indicate that monocyte differentiation involves enhancement of IRES activity, by which protein levels of AMAP1 are primarily upregulated.
Miyata
Mariko
M
Department of Molecular Biology, Osaka Bioscience Institute, Suita, Osaka, Japan.
Raven
Jennifer F
JF
Baltzis
Dionissios
D
Koromilas
Antonis E
AE
Sabe
Hisataka
H
D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D014176:Protein Biosynthesis; D020298:U937 Cells
D020121:5' Untranslated Regions; D002352:Carrier Proteins; C465633:MYCBPAP protein, human