Functional characterization of the candidate tumor suppressor gene NPRL2/G21 located in 3p21.3C

Cancer Research
Jingfeng LiEugene Zabarovsky

Abstract

Initial analysis identified the NPRL2/G21 gene located in 3p21.3C, the lung cancer region, as a strong candidate tumor suppressor gene. Here we provide additional evidence of the tumor suppressor function of NPRL2/G21. The gene has highly conserved homologs/orthologs ranging from yeast to humans. The yeast ortholog, NPR2, shows three highly conserved regions with 32 to 36% identity over the whole length. By sequence analysis, the main product of NPRL2/G21 encodes a soluble protein that has a bipartite nuclear localization signal, a protein-binding domain, similarity to the MutS core domain, and a newly identified nitrogen permease regulator 2 domain with unknown function. The gene is highly expressed in many tissues. We report inactivating mutations in a variety of tumors and cancer cell lines, growth suppression of tumor cells with tet-controlled NPRL2/G21 transgenes on plastic Petri dishes, and suppression of tumor formation in SCID mice. Screening of 7 renal, 5 lung, and 7 cervical carcinoma cell lines showed homozygous deletions in the 3' end of NPRL2 in 2 renal, 3 lung, and 1 cervical (HeLa) cell line. Deletions in the 3' part of NPRL2 could result in improper splicing, leading to the loss of the 1.8 kb functional NPRL2 mR...Continue Reading

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Citations

Apr 24, 2009·Cancer Chemotherapy and Pharmacology·Zhu YuanXia Zhao
Jun 1, 2013·Science·Reuben J Shaw
Aug 30, 2008·PloS One·Fuli WangEugene R Zabarovsky
May 30, 2009·PloS One·Vladimir I KashubaEugene R Zabarovsky
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