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[A. Biochemistry/Molecular Biology] A-13

The API5-FGF2 complex functions in mRNA export and is a

potential target for cancer therapeutics

SeonJeong Baek¹, Seoung Min Bong¹, Byung Il Lee¹*

¹Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang-si

10408, Korea

API5 (APoptosis Inhibitor 5) and nuclear FGF2 (Fibroblast Growth Factor 2) are upregulated in various human cancers

and are correlated with poor prognosis. Here, we determined the crystal structure of the API5–FGF2 complex and
identified critical residues driving the protein interaction. This provided structural basis of nuclear localization of the

FGF2 isoform lacking canonical nuclear localization signal and identified cryptic nuclear localization sequence in
FGF2. The interaction between API5 and FGF2 was important for mRNA export and regulate the export of bulk

mRNA and specific mRNAs containing eIF4E sensitivity elements. Interestingly, API5–FGF2 complex directly
interacted with UAP56, a common factor of these two mRNA export complexes. Disruption of the API5–FGF2

interaction reduced cell proliferation and increased drug sensitivity. These data reveal a previously unknown function
for API5 and nuclear FGF2 and suggest a new therapeutic target for regulating the expression of oncogenes at the

mRNA export level. REFERENCES 1. Tewari,M., Yu,M., Ross,B., Dean,C., Giordano,A. and Rubin,R.(1997) AAC-11, a
novel cDNA that inhibits apoptosis after growth factor withdrawal. Cancer Res., 57, 4063–4069.

ACKNOWLEDGMENTS We thank the beamline staff of Pohang Light Source (Beamline 7A) for their assistance during
X-ray data collection.