The connexin43-interacting protein of 75kDa (CIP75) mediates the endoplasmic reticulum dislocation of connexin43

Gap junctions are intercellular channels comprised of connexin proteins, such as connexin43 (Cx43). The level of gap junctional intercellular communication can be regulated by Cx43 turnover mediated through various degradation pathways. The UbL (ubiquitin-like domain)-UBA (ubiquitin-associated domain) protein, CIP75, regulates the proteasomal degradation of Cx43. Subcellular fractionation studies indicated that CIP75 interacts with Cx43 that is localized to the membrane of the endoplasmic reticulum (ER). This Cx43-CIP75 complex also contained the proteasomal subunits S2/Rpn1 and S5a/Rpn10, as demonstrated by co-immunoprecipitation. The deliberate misfolding of Cx43, induced by DTT, lead to enhanced CIP75 binding. Reducing CIP75 levels by shRNA-mediated knockdown diminished the association of Cx43 with the proteasome, but still allowed Cx43 ER dislocation and degradation. These results suggested that CIP75 is essential for the interaction of Cx43 and the proteasome, but that alternate compensatory mechanisms exist to supplement the degradation normally facilitated by CIP75.

Source: BJ Cell - November 20, 2013 Category: Biochemistry Authors: V Su, C Hoang, D Geerts, A F. Lau Tags: BJ Cell Source Type: research