Aggregation and retention of human urokinase type plasminogen activator in the yeast endoplasmic reticulum.

ABSTRACT:

Background

Secretion of recombinant proteins in yeast can be affected by their improper folding in the endoplasmic reticulum and subsequent elimination of the misfolded molecules via the endoplasmic reticulum associated protein degradation pathway. Recombinant proteins can also be degraded by the vacuolar protease complex. Human urokinase type plasminogen activator (uPA) is poorly secreted by yeast but the mechanisms interfering with its secretion are largely unknown.

Results

We show that in Hansenula polymorpha overexpression worsens uPA secretion and stimulates its intracellular aggregation. The absence of the Golgi modifications in accumulated uPA suggests that aggregation occurs within the endoplasmic reticulum. Deletion analysis has shown that the N-terminal domains wer

SUBMITTER: Agaphonov MO 

PROVIDER: S-EPMC130179 | biostudies-literature | 2002 Oct

REPOSITORIES: biostudies-literature