Tumor suppressor BAP1 nuclear import is governed by transportin-1.

Subcellular localization of the deubiquitinating enzyme BAP1 is deterministic for its tumor suppressor activity. While the monoubiquitination of BAP1 by an atypical E2/E3-conjugated enzyme UBE2O and BAP1 auto-deubiquitination are known to regulate its nuclear localization, the molecular mechanism by which BAP1 is imported into the nucleus has remained elusive. Here, ...
we demonstrated that transportin-1 (TNPO1, also known as Karyopherin ?2 or Kap?2) targets an atypical C-terminal proline-tyrosine nuclear localization signal (PY-NLS) motif of BAP1 and serves as the primary nuclear transporter of BAP1 to achieve its nuclear import. TNPO1 binding dissociates dimeric BAP1 and sequesters the monoubiquitination sites flanking the PY-NLS of BAP1 to counteract the function of UBE2O that retains BAP1 in the cytosol. Our findings shed light on how TNPO1 regulates the nuclear import, self-association, and monoubiquitination of BAP1 pertinent to oncogenesis.
Mesh Terms:
Active Transport, Cell Nucleus, Cell Nucleus, Humans, Nuclear Localization Signals, Proline, Tumor Suppressor Proteins, Tyrosine, Ubiquitin Thiolesterase, Ubiquitin-Conjugating Enzymes, beta Karyopherins
J Cell Biol
Date: Dec. 06, 2021
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