Compositions and Methods For the Modulation of Ras Proteins

A method for decreasing proliferation and/or migration of a cancer cell comprising a Ras protein, the method comprising:

• contacting the cell with an agent, wherein the agent interferes with sumoylation of the Ras protein at amino acid residue 42 by a SUMO protein.

A method for decreasing sumoylation of a Ras protein by a small ubiquitin-like modifier (SUMO) protein, the method comprising:

• introducing a first point mutation at amino acid residue 42 of the Ras protein to form a modified Ras protein.

A modified Ras protein comprising the amino acid sequence set forth in SEQ ID NO:

• 2 comprising a point mutation at amino acid residue 42 of SEQ ID NO:2.

A modified Ras protein comprising the amino acid sequence set forth in SEQ ID NO:

• 2 comprising the following mutations:
• (i) a first point mutation at amino acid residue 42 of SEQ ID NO:2 substituted with an amino acid other than Lysine;
• and (ii) a second point mutation at amino acid residue 12 of SEQ ID NO:2 substituted with a valine or an amino acid other than glycine, at amino acid residue 13 of SEQ ID NO:2 substituted with an amino acid other than glycine, at amino acid residue 17 of SEQ ID NO:2 substituted with asparagine or an amino acid other than serine, at amino acid residue 61 of SEQ ID NO:2 substituted with an amino acid other than glutamine, and/or at amino acid residue 119 of SEQ ID NO:2 substituted with asparagine or an amino acid other than aspartic acid.