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Figure 10 | BMC Cell Biology

Figure 10

From: A STAT3-decoy oligonucleotide induces cell death in a human colorectal carcinoma cell line by blocking nuclear transfer of STAT3 and STAT3-bound NF-κB

Figure 10

Nucleo-cytoplasmic shuttling of STAT3, and putative mechanism of action of STAT3-decoy ODN. A: Nucleo-cytoplasmic shuttling of activated STAT3. Phosphorylation of STAT3 on tyrosine 705 by the JAK family kinases results in dimerization and interaction with importins (imp), followed by transfer to the nucleus through the nuclear pore complex (NPC). Phospho-STAT3 binds its DNA targets, this is followed by dephosphorylation by a nuclear tyrosine phosphatase. Unphosphorylated STAT3 re-enters the cytoplasm: this depends in part on CRM1, which is inhibited by leptomycin B (LMB). Tyrosine phosphatases which dephosphorylate activated JAKs and phospho-STAT3 are inhibited by sodium vanadate (VO4). Stattic interaction with STAT3 monomers prevents dimerization and nuclear entry. STAT3-decoy ODN (decoy) interaction with active phosphorylated STAT3 dimers is suggested to compete with importin, thereby trapping active STAT3 in the cytoplasm. B: Nucleo-cytoplasmic cycling of activated and non-activated STAT3. Non-activated STAT3 cycles in and out of the nucleus in the absence of activation (phosphorylation: +P) (1, blue arrows). Activated STAT3 enters the nucleus by a transporter-mediated process (1, red arrow) and returns to the cytoplasm following dephosphorylation: -P) (1, yellow arrow). In STAT3-decoy ODN-transfected cells, cycling of non-activated STAT3 is unchanged (2, blue arrows), whereas activated (phosphorylated) STAT3 does not enter the nucleus (2, red arrow). NPC: nuclear pore complex. The scheme in B is adapted from a figure of ref.[3].

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