A Lipid Transfer Protein Signaling Axis Exerts Dual Control of Cell-Cycle and Membrane Trafficking Systems.
Dev Cell
; 44(3): 378-391.e5, 2018 02 05.
Article
in En
| MEDLINE
| ID: mdl-29396115
ABSTRACT
Kes1/Osh4 is a member of the conserved, but functionally enigmatic, oxysterol binding protein-related protein (ORP) superfamily that inhibits phosphatidylinositol transfer protein (Sec14)-dependent membrane trafficking through the trans-Golgi (TGN)/endosomal network. We now report that Kes1, and select other ORPs, execute cell-cycle control activities as functionally non-redundant inhibitors of the G1/S transition when cells confront nutrient-poor environments and promote replicative aging. Kes1-dependent cell-cycle regulation requires the Greatwall/MASTL kinase ortholog Rim15, and is opposed by Sec14 activity in a mechanism independent of Kes1/Sec14 bulk membrane-trafficking functions. Moreover, the data identify Kes1 as a non-histone target for NuA4 through which this lysine acetyltransferase co-modulates membrane-trafficking and cell-cycle activities. We propose the Sec14/Kes1 lipid-exchange protein pair constitutes part of the mechanism for integrating TGN/endosomal lipid signaling with cell-cycle progression and hypothesize that ORPs define a family of stage-specific cell-cycle control factors that execute tumor-suppressor-like functions.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Saccharomyces cerevisiae
/
Receptors, Steroid
/
Cell Cycle
/
Cell Membrane
/
Saccharomyces cerevisiae Proteins
/
Phospholipid Transfer Proteins
/
Histone Acetyltransferases
/
Golgi Apparatus
/
Lipids
/
Membrane Proteins
Type of study:
Prognostic_studies
Language:
En
Journal:
Dev Cell
Journal subject:
EMBRIOLOGIA
Year:
2018
Document type:
Article
Affiliation country:
Estados Unidos