Investigation of the Canonical vs. Non-Canonical Start Codons in the Human Clusterin Gene, Poster 53

Clusterin (CLU), also known as Apolipoprotein J (ApoJ) is a highly glycosylated extracellular chaperone. In humans it is expressed from a broad spectrum of tissues and related to a plethora of physiological and... [ view full abstract ]

Clusterin (CLU), also known as Apolipoprotein J (ApoJ) is a highly glycosylated extracellular chaperone. In humans it is expressed from a broad spectrum of tissues and related to a plethora of physiological and pathophysiological processes, such as Alzheimer's disease, atherosclerosis and cancer. In its dominant form it is expressed as a secretory protein (secreted CLU, sCLU). During its maturation, the sCLU-precursor is N-glycosylated and cleaved into an α- and a β-chain, which are connected by five symmetrical disulfide bonds. Recently, it has been demonstrated that besides the predominant sCLU, rare intracellular CLU forms are expressed in stressed cells. Since these forms do not enter or complete the secretory pathway, they are not proteolytically modified and show either no or only core glycosylation. Due to their sparsity, the mechanism for the intracellular CLU expression is poorly understood; the human CLU gene encodes at least 3 different pre-mRNAs resulting in at least 4 different mRNAs. To evaluate the expression of intracellular CLU, we investigate two start codons found within the CLU gene. One has been previously suggested as a canonical start site for sCLU. The other we investigate as a non-canonical start site for intracellular CLU based off of post-transcriptional modification data.