INVESTIGADORES
ADAMO Ana Maria
artículos
Título:
The Growth Associated Protein (GAP-43) is degraded via the Ubiquitin-Protesome System
Autor/es:
DE MOLINER, K; WOLFSON, M.; E; PERRONE-BIZZOZERO, N; ADAMO, A.M.
Revista:
JOURNAL OF NEUROSCIENCE RESEARCH
Editorial:
Wiley-Lis inc.
Referencias:
Lugar: Indianapolis; Año: 2005 vol. 79 p. 652 - 660
ISSN:
0360-4012
Resumen:
Growth-associated protein-43 (GAP-43) is a phosphoprotein
whose expression in neurons is related to the
initial establishment and remodeling of neural connections.
GAP-43 gene expression is known to be regulated
at both the transcriptional and the postranscriptional levels.
However, very little is known about the cellular mechanism
involved in the degradation of this protein. Ubiquitin
(Ub) is well known for its role in targeting cytoplasmic
proteins for degradation by the 26S proteasome.
The ubiquitin-proteasome system (UPS) consists of a
conserved cascade of three enzymatic components that
attach Ub covalently to various substrates and control
the degradation of protein involved in several important
cellular processes. In this study, we investigated the
degradation of GAP-43 in transfected NIH 3T3 cells and
neuronal cultures. We found that the proteasome inhibitors
lactacystin and MG132 increased the cellular
GAP-43 level, leading to the accumulation of polyubiquitinated
forms of this protein in transfected cells and
that the Ub-proteasome pathway is also involved in the
turnover of this protein in neurons. We conclude based
on our findings that GAP-43 is a substrate of the UPS.