The role of a newly identified SET domain-containing protein, SETD3, in oncogenesis.
The SET domain is found in histone methyltransferases and other lysine methyltransferases. SET domain-containing proteins such as MLL1 play a critical role in leukemogenesis, while others such as SETD2 may function as a tumor suppressor in breast cancer and renal cell carcinoma. We recently discovered that SETD3, a well-conserved SET domain-containing protein, was involved in a translocation to the immunoglobulin lambda light chain locus in one of the non-homologous end-joining/p53-deficient peripheral B-cell lymphomas. We showed that a truncated mRNA lacking the SET domain sequences in Setd3 gene was highly expressed in the lymphoma. Furthermore, we found that the truncated SET-less protein displayed oncogenic potential while the full length SETD3 protein did not. Finally, SETD3 exhibits histone methyltransferases activity on nucleosomal histone 3 in a SET-domain dependent manner. We propose that this newly identified Setd3 gene may play an important role in carcinogenesis.
Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO, USA.
Zhangguo
Z
Chen
Catherine T
CT
Yan
Yali
Y
Dou
Sawanee S
SS
Viboolsittiseri
Jing H
JH
Wang
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D059766:DNA End-Joining Repair; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D051379:Mice; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency
D006657:Histones; D016159:Tumor Suppressor Protein p53; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C584641:SETD3 protein, human