Hyperactive Ras disrupts cell size control and a key step in cell cycle entry in budding yeast

Area of Science:

• Cell Biology
• Molecular Biology
• Oncology

Background:

• Cancer cells exhibit universal cell size defects, but causes are unknown.
• Hyperactive Ras oncogenes, analogous to yeast ras2G19V, are linked to cell size abnormalities.

Purpose of the Study:

• Investigate mechanisms by which ras2G19V influences cell size in yeast.
• Elucidate Ras signaling pathways controlling cell cycle entry and cyclin gene expression.

Main Methods:

• Yeast genetics and molecular biology techniques.
• Analysis of cell cycle progression and gene transcription.
• Investigated Ras signaling pathways, including PKA-independent mechanisms.

Main Results:

• Ras2G19V inhibits cell cycle entry by preventing Cln3-induced transcription of late G1 cyclins.
• Overexpression of Cln3 due to ras2G19V leads to delayed cell cycle entry and larger cell size.
• Ras2G19V signaling impacts Whi5 repressor inactivation via PKA-independent pathways.

Conclusions:

• Ras signaling critically regulates cell cycle entry and cell size through cyclin gene transcription.
• Identified novel PKA-independent mechanisms by which Ras influences G1 cyclin expression.
• Yeast Ras signaling provides a model for understanding Ras-mediated cell size control in mammalian cancers.