Distinct domain utilization by Smad3 and Smad4 for nucleoporin interaction and nuclear import.
Smad proteins undergo rapid nuclear translocation upon stimulation by transforming growth factor-beta (TGFbeta) and in so doing transduce the signal into the nucleus. In this report we unraveled nuclear import mechanisms of Smad3 and Smad4 that are dependent on their interaction with FG-repeat-containing nucleoporins such as CAN/Nup214, without the involvement of importin molecules that are responsible for most of the known nuclear import events. A surface hydrophobic corridor within the MH2 domain of Smad3 is critical for association with CAN/Nup214 and nuclear import, whereas Smad4 interaction with CAN/Nup214, and nuclear import requires structural elements present only in the full-length Smad4. As exemplified by the different susceptibility to inhibition of import by cytoplasmic retention factor SARA (Smad anchor for receptor activation), such utilization of distinct domains for nuclear import of Smad3 and Smad4 suggests that nuclear transport of Smad3 and Smad4 is subject to control by different retention factors.
Xu
Lan
L
Cell Biology Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Alarcón
Claudio
C
Cöl
Seda
S
Massagué
Joan
J
D021581:Active Transport, Cell Nucleus; D001665:Binding Sites; D002352:Carrier Proteins / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D047908:Intracellular Signaling Peptides and Proteins; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid; D012697:Serine Endopeptidases; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; C116420:ZFYVE16 protein, human; D012697:Serine Endopeptidases