Methods of modulating smyd3 for treatment of cancer

A method of screening for a compound for treating a cancer selected from group consisting of colorectal cancer, hepatocellular carcinoma, bladder cancer, and breast cancer, said method comprising the steps of:

• a. identifying a test compound that modulates methylation of a retinoblastoma peptide by SMYD3 according to a method comprising the steps of:
• 1) 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;
• vi. 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;
• 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 a retinoblastoma peptide to be methylated and a cofactor in the presence of the test compound under conditions suitable for methylation of the retinoblastoma peptide;
• 2) detecting the methylation level of the retinoblastoma peptide;
• and
• 3) comparing the methylation level of step 2) with a control level detected in the absence of the test compound, and
• b. selecting the test compound that decreases the methylation level of the retinoblastoma peptide to be methylated as compared to a control methylation level detected in the absence of the test compound.