TY - JOUR
T1 - Nuclear-cytosolic transport of COMMD1 regulates NF-kappaB and HIF-1 activity
AU - Muller, Patricia A. J.
AU - van de Sluis, Bart
AU - Groot, Arjan J.
AU - Verbeek, Dineke
AU - Vonk, Willianne I. M.
AU - Maine, Gabriel N.
AU - Burstein, Ezra
AU - Wijmenga, Cisca
AU - Vooijs, Marc
AU - Reits, Eric
AU - Klomp, Leo W. J.
PY - 2009
Y1 - 2009
N2 - COMMD1 is a novel inhibitor of the transcription factors NF-kappaB and HIF-1, which play important roles in inflammation and tumor growth, respectively. In this study, we identified two highly conserved nuclear export signals (NESs) in COMMD1 and revealed that these NESs were essential and sufficient to induce maximal nuclear export of COMMD1. Inhibition of CRM1-mediated nuclear export by Leptomycin B resulted in nuclear accumulation of COMMD1. In addition, low oxygen concentrations induced the active export of COMMD1 from the nucleus in a CRM1-dependent manner. Disruption of the NESs in COMMD1 increased the repression of COMMD1 on transcriptional activity of NF-kappaB and HIF-1. In conclusion, these data indicate that COMMD1 undergoes constitutive nucleocytoplasmic transport as a novel mechanism to regulate NF-kappaB and HIF-1 signaling
AB - COMMD1 is a novel inhibitor of the transcription factors NF-kappaB and HIF-1, which play important roles in inflammation and tumor growth, respectively. In this study, we identified two highly conserved nuclear export signals (NESs) in COMMD1 and revealed that these NESs were essential and sufficient to induce maximal nuclear export of COMMD1. Inhibition of CRM1-mediated nuclear export by Leptomycin B resulted in nuclear accumulation of COMMD1. In addition, low oxygen concentrations induced the active export of COMMD1 from the nucleus in a CRM1-dependent manner. Disruption of the NESs in COMMD1 increased the repression of COMMD1 on transcriptional activity of NF-kappaB and HIF-1. In conclusion, these data indicate that COMMD1 undergoes constitutive nucleocytoplasmic transport as a novel mechanism to regulate NF-kappaB and HIF-1 signaling
U2 - https://doi.org/10.1111/j.1600-0854.2009.00892.x
DO - https://doi.org/10.1111/j.1600-0854.2009.00892.x
M3 - Article
C2 - 19220812
SN - 1398-9219
VL - 10
SP - 514
EP - 527
JO - Traffic (Copenhagen, Denmark)
JF - Traffic (Copenhagen, Denmark)
IS - 5
ER -