A conserved pathway that controls c-Myc protein stability through opposing phosphorylation events occurs in yeast.
The c-Myc transcription factor is a key regulator of cell proliferation and cell fate decisions. c-Myc overexpression is observed in a variety of human tumors, revealing the importance of maintaining normal levels of c-Myc protein. c-Myc protein stability in mammalian cells is controlled by interdependent and sequential phosphorylation and dephosphorylation events on two highly conserved residues, serine 62 and threonine 58. Here we show that these sequential phosphorylation and dephosphorylation events and their effect on c-Myc stability also occurs in the model system Saccharomyces cerevisiae. These results suggest the presence of a conserved pathway in yeast that controls protein turnover in response to a specific phospho-degron sequence. These findings have implications regarding conserved pathways for regulated protein degradation, and they validate the use of genetically tractable yeast for the study of the turnover of proteins such as c-Myc that contain this motif.
Escamilla-Powers
Julienne R
JR
Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, Oregon 97239, USA.
Sears
Rosalie C
RC
D020816:Amino Acid Motifs / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D016271:Proto-Oncogene Proteins c-myc; D029701:Saccharomyces cerevisiae Proteins