Dosage sensitivity of JDPs, a valuable tool for understanding their function: a case study on Caj1 overexpression-mediated filamentous growth in budding yeast.
Curr Genet
; 67(3): 407-415, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-33492464
ABSTRACT
J-domain proteins (JDPs) partner with Hsp70s to oversee proper synthesis, folding, transport and turnover of proteins in the cell. In any subcellular compartment, often multiple JDPs collaborate with a single Hsp70 to perform a variety of functions. Being co-localized, JDPs may exhibit complex genetic and physical interactions with each other, their clients as well as the Hsp70 partners. Even though most JDPs are highly specialized, redundancy between them is possible, making their functional analysis challenging. In the absence of assayable deletion phenotypes, protein overexpression appears to be a powerful alternative strategy to study JDP function. Here, we show that high levels of Caj1, one of the cytosolic JDPs, cause filamentous growth and G2/M arrest in yeast cells. Mutation in the critical HPD motif in the J-domain of Caj1 completely abolished these phenotypes, suggesting that Hsp70 co-chaperone function is important for the dominant-negative phenotypes exhibited by Caj1 overexpression. In this paper, we discuss the possible underlying mechanisms responsible for the pleiotropic phenotypes displayed by Caj1 overexpression in the light of current models proposed for dosage-sensitive genes (DSGs). Finally, we present generalized mechanisms of JDP overexpression-mediated dominant-negative phenotypes in budding yeast.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a Calmodulina
/
Chaperonas Moleculares
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Proteínas de Choque Térmico HSP70
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Proteínas de Saccharomyces cerevisiae
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Proteínas de Choque Térmico HSP40
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Curr Genet
Ano de publicação:
2021
Tipo de documento:
Article