Methods of modulating SMYD3 for treatment of cancer

A method for identifying an agent that modulates methylation of a retinoblastoma peptide by SMYD3, said method comprising the steps of:

• a. contacting an SMYD3 polypeptide having a methyltransferase activity selected from the group consisting of:
• i. a polypeptide comprising the amino acid sequence of SEQ ID NO:
• 2;
• ii. a polypeptide that comprises the amino acid sequence of positions 117 to 246 of the amino acid sequence of SEQ ID NO:
• 2, wherein said polypeptide has a methyltransferase activity equivalent to the polypeptide consisting of the amino acid sequence of SEQ ID NO:2;
• iii. a polypeptide that comprises the amino acid sequence of positions 1 to 250 of the amino acid sequence of SEQ ID NO:
• 2;
• iv. a polypeptide that comprises the amino acid sequence of positions 45 to 428 of the amino acid sequence of SEQ ID NO:
• 2;
• v. a polypeptide that comprises the amino acid sequence of SEQ ID NO:
• 2 in which the amino acids of positions 1 to 30 have been deleted;
• vi. a polypeptide that comprises the amino acid sequence of SEQ ID NO:
• 2 in which the amino acids of positions 1 to 44 are deleted;
• vii. a polypeptide that comprises the amino acid sequence of SEQ ID NO:
• 2 in which the amino acids of positions 1 to 20 are deleted;
• and
• viii. a polypeptide that comprises the amino acid sequence of SEQ ID NO:
• 2 in which the amino acids of positions 1 to 10 are deleted;
• with the retinoblastoma peptide to be methylated and a cofactor in the presence of the agent under conditions suitable for methylation of the retinoblastoma peptide;
• b. detecting the methylation level of the retinoblastoma peptide;
• and
• c. comparing the methylation level of step (b) with a control level detected in the absence of the agent,
• wherein an increase or decrease in the methylation level compared to the control level indicates that the agent modulates the methylation of the retinoblastoma peptide by SMYD3.