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. 2020 Jul 21;21(14):5164. doi: 10.3390/ijms21145164

Figure 3.

Figure 3

p65 shuttling and the current therapeutic targets explored in the pathway. After ubiquitination IkB, translocation of p65/p50 (Cargo) happens via arginine and lysine-rich NLS (Nuclear localization signals) of p65 interaction with importin α/β heterodimer. This trimeric protein complex (cNLS/importin α/β protein) ferrying into the nucleus is facilitated through importin β interaction with nuclear pore complexes (NPCs). Whereas export of p65 via the CRM1-dependent pathway upon interaction with leucine-rich NES. CRM1 is an export receptor, facilitates the transport of large macromolecules including RNA and protein from the nuclear membrane to the cytoplasm. CRM1 binds the Ran protein bound to GTP, allowing for a conformational change that facilitates cargo protein to nuclear export. Nuclear import and export inhibitors preclude the p65 shuttling via NLS and NES, respectively.