hnRNP L enhances sensitivity of the cells to KW-2189.
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved in several RNA-related biological processes. We demonstrated hnRNP L as a candidate protein of DARP (duocarmycin-DNA adduct recognizing protein) by gel shift assay and amino acid sequencing. Stable transfectants of hnRNP L showed high sensitivity of the cells to the growth inhibitory effect of KW-2189, a duocarmycin derivative in vitro. Immunostaining of hnRNP L demonstrated differential intracellular localization of hnRNP L among human lung cancer cell lines. A transfection study using a series of deletion mutants of hnRNP L fused to indicated that the N-terminal portions of RRM(RNA recognition motif)1, RRM3 and RRM2 are involved in localization of hnRNP L. We identified sequences in these portions that have high homology with the sequences of known NLS (nuclear localization signal) and NES (nuclear export signal). hnRNP L is a factor that determines the sensitivities of cancer cells to the minor groove binder, and overexpression and differential intracellular localization of hnRNP L are involved in its function in lung cancer.
Taguchi
Fumiko
F
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
Kusaba
Hitoshi
H
Asai
Akira
A
Iwamoto
Yasuo
Y
Yano
Keiichi
K
Nakano
Hirofumi
H
Mizukami
Tamio
T
Saijo
Nagahiro
N
Kato
Harubumi
H
Nishio
Kazuto
K
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D000080890:Duocarmycins; D034664:Heterogeneous-Nuclear Ribonucleoprotein L / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D012261:Ribonucleoproteins; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D000080890:Duocarmycins; C400563:HNRNPL protein, human; D034664:Heterogeneous-Nuclear Ribonucleoprotein L; D009687:Nuclear Proteins; D011760:Pyrrolidinones; D012261:Ribonucleoproteins; C086920:KW 2189