Nucleotide Alteration of Retinoblastoma Protein-Interacting Zinc Finger Gene, RIZ, in Human Leukemia

Nucleotide Alteration of Retinoblastoma Protein-Interacting
Zinc Finger Gene, RIZ, in Human Leukemia

OSAMU SASAKI, KUNIAKI MEGURO, YASUO TOHMIYA, TADAO FUNATO,¹
SHIGEKI SHIBAHARA² and TAKESHI SASAKI

Department of Rheumatology and Hematology, ¹Department of Molecular Diagnosis, and ²Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai 980-8574

The retinoblastoma protein-interacting zinc finger gene (RIZ) is a zinc-finger type DNA binding protein and is postulated as a member of the nuclear protein-methyltransferase superfamily. RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the N-terminal PR (PRDI-BF1 and RIZ homologous)-domain, RIZ2 lacks it. RIZ1 is now considered as a tumor suppressor. We analyzed nucleotide alteration of RIZ gene in human leukemia. The results revealed a single nucleotide polymorphism (SNP), T¹⁷⁰⁴ to A, near the conserved Rb-binding domain, leading to an amino acid change, Asp²⁸³ to Glu. Interestingly, 17 of 21 leukemia cell lines are homozygous for the T¹⁷⁰⁴ allele whereas only 2 of 20 normal subjects are homozygous for the allele. In addition, one base pair deletion in the poly (A)₉ tract in the coding region near the C-terminal zinc-fingers was identified, resulting in frameshift, in 1 out of 17 leukemia cell lines, but no mutation in samples from 15 patients with acute lymphoblastic leukemia (ALL) and 6 patients with adult T cell leukemia (ATL). In the PR or SH3 (src homology 3) domain of the RIZ gene, no mutation was found. These findings suggest that RIZ may be a possible target of structural alteration leading to leukemia.

Keywords —— human leukemia; RIZ; tumor suppressor gene; gene mutation; SNP

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Tohoku J. Exp. Med., 2002, 196, 193-201

Address for reprints Kuniaki Meguro M.D., Ph.D., Department of Rheumatology and Hematology, Tohoku University School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan.

e-mail: mekuak@mail.cc.tohoku.ac.jp or kuniakim@rd6.so-net.ne.jp