Novel phosducin‐like protein 1 interactions

Abstract

Phosducin‐like protein 1 (PhLP1) has been recently shown tobe a co‐chaperone with the cytosolic chaperonin complex (CCT) in the folding and assembly of nascentG protein βγ subunit dimers and Gβ5‐RGS proteins. However, other possible functions for PhLP1 either as a co‐chaperone or otherwise are yet to be investigated. Using PhLP1 as bait, a co‐immunoprecipitation proteomics screen indicated that PhLP1 interacted with programmed cell death 5 protein (PDCD5) and hydroxysteroid (17β) dehydrogenase 4 (HSD17B4). PDCD5 is a known tumor suppressor which is down‐regulated in several tumor types and is found to translocate rapidly from the cytoplasm to the nucleus during the initial stages of apoptosis. HSD17B4 is involved in the beta‐oxidation pathway for fatty acids and is implicated in D‐bifunctional protein deficiency. Subsequent binding experiments have validated both the PhLP1‐PDCD5 and PhLP1‐HSD17B4 interactions and revealed that both proteins interacted specifically with PhLP1 and not other members of the phosducin family of proteins. Additional experiments have shown a strong interaction between PDCD5 and CCT which was inhibited in the presence of PhLP1. The current study addresses the questions raised by these interactions. Namely, do PDCD5 and HSD17B4 require the assistance of the PhLP1‐CCT co‐chaperone complex to fold properly or are the proteins interacting for other purposes?