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Prohormone convertase 1 (PC1) processing and sorting: effect of PC1 propeptide and proSAAS
Sang-Nam Lee1, Emmanuel Prodhomme, Iris Lindberg
1Louisiana State University Health Sciences Center, Department of Biochemistry and Molecular Biology, 1901 Perdido Street, New Orleans, Louisiana 70112, USA.
The Journal of Endocrinology
|July 31, 2004
Summary
The prohormone convertase 1 (PC1) propeptide inhibits PC1 activity and proopiomelanocortin (POMC) processing. However, chimeric constructs containing the propeptide and SAAS CT peptide are ineffective inhibitors of precursor maturation.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Endocrinology
Background:
- Prohormone convertase 1 (PC1) is a key enzyme in the regulated secretory pathway, processing precursor proteins.
- PC1 activity may be modulated by endogenous inhibitors like its propeptide and proSAAS.
Purpose of the Study:
- To investigate the inhibitory effects of proSAAS and propeptide-containing constructs on PC1 processing and activity.
- To elucidate the roles of the PC1 propeptide and SAAS CT peptide in regulating PC1 function.
Main Methods:
- Pulse-chase experiments in AtT-20 cells to assess PC1 and proopiomelanocortin (POMC) processing.
- Transient expression of PC1 and various constructs in HEK293 cells.
Main Results:
- ProSAAS expression inhibited PC1 and POMC processing in AtT-20 cells.
- A construct with the PC1 propeptide alone inhibited PC1 and POMC processing.
- The SAAS CT peptide portion of a chimera inhibited PC1 zymogen and C-terminal processing in HEK293 cells.
Conclusions:
- The PC1 propeptide, when expressed in trans, acts as an endogenous inhibitor of PC1.
- Chimeric constructs containing the SAAS CT peptide and propeptide are not effective inhibitors of precursor maturation in the regulated pathway.