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J Cell Biol

Title:		Activation of an MAP kinase cascade leads to Sir3p hyperphosphorylation and strengthens transcriptional silencing
Author(s):		Stone EM; Pillus L;
Address:		"Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347, USA"
Journal Title:		J Cell Biol
Year:		1996
Volume:		135
Issue:		3
Page Number:		571 - 583
DOI:		10.1083/jcb.135.3.571
ISSN/ISBN:		0021-9525 (Print) 1540-8140 (Electronic) 0021-9525 (Linking)
Abstract:		"During cell division and growth, the nucleus and chromosomes are remodeled for DNA replication and cell type-specific transcriptional control. The yeast silencing protein Sir3p functions in both chromosome structure and in transcriptional regulation. Specifically, Sir3p is critical for the maintenance of telomere structure and for transcriptional repression at both the silent mating-type loci and telomeres. We demonstrate that Sir3p becomes hyperphosphorylated in response to mating pheromone, heat shock, and starvation. Cells exposed to pheromone arrest in G1 of the cell cycle, yet G1 arrest is neither necessary nor sufficient for pheromone-induced Sir3p hyperphosphorylation. Rather, hyperphosphorylation of Sir3p requires the mitogen-activated protein (MAP) kinase pathway genes STE11, STE7, FUS3/KSS1, and STE12, indicating that an intact signal transduction pathway is crucial for this Sir3p phosphorylation event. Constitutive activation of the pheromone-response MAP kinase cascade in an STE11-4 strain leads to hyperphosphorylation of Sir3p and increased Sir3p-dependent transcriptional silencing at telomeres. Regulated phosphorylation of Sir3p may thus be a mechanistically significant means for modulating silencing. Together, these observations suggest a novel role for MAP kinase signal transduction in coordinating chromatin structure and nuclear organization for transcriptional silencing"
Keywords:		"Calcium-Calmodulin-Dependent Protein Kinases/genetics/*metabolism/physiology Enzyme Activation Fungal Proteins/*metabolism G1 Phase Gene Expression Regulation, Fungal/physiology Heat-Shock Response/physiology Mating Factor Mutation Peptides/pharmacology P;"
Notes:		"MedlineStone, E M Pillus, L eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 1996/11/01 J Cell Biol. 1996 Nov; 135(3):571-83. doi: 10.1083/jcb.135.3.571"