Nuclear-Cytosolic Transport of COMMD1 Regulates NF-kappa B and HIF-1 Activity

作者：Muller Patricia A J; van de Sluis Bart; Groot Arjan J; Verbeek Dineke; Vonk Willianne I M; Maine Gabriel N; Burstein Ezra; Wijmenga Cisca; Vooijs Marc; Reits Eric; Klomp Leo W J^*

来源：Traffic, 2009, 10(5): 514-527.

DOI：10.1111/j.1600-0854.2009.00892.x

• COMMD1
• HIF-1
• hypoxia
• NF-kappa B
• nuclear export signal

Copper metabolism MURR1 domain1 (COMMD1) is a novel inhibitor of the transcription factors NF-kappa B 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 in transcriptional activity of NF-kappa B and HIF-1. In conclusion, these data indicate that COMMD1 undergoes constitutive nucleocytoplasmic transport as a novel mechanism to regulate NF-kappa B and HIF-1 signaling.

• 出版日期2009-5