Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism

Hisanobu Oda, Akinobu Taketomi, Riichiroh Maruyama, Riyoko Itoh, Kenichi Nishioka, Hiroyuki Yakushiji, Tomokazu Suzuki, Mutsuo Sekiguchi, Yusaku Nakabeppu

研究成果: Contribution to journalArticle査読

39 被引用数 (Scopus)

抄録

The human MTH1 gene for 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase, produces seven types (types 1, 2A, 2B, 3A, 3B, 4A and 4B) of mRNAs. The B-type mRNAs with exon 2b-2c segments have three additional in-frame AUGs in their 5' regions. We report here that these transcripts produce three forms of MTH1 polypeptides (p22, p21 and p18) in in vitro translation reactions. Three polypeptides were also detected in extracts of human cells, using western blotting. B-type mRNAs with a polymorphic alteration (GU→GC) at the beginning of exon 2c that converts an in-frame UGA to CGA yielding another in-frame AUG further upstream, produced an additional polypeptide (p26) in vitro. Substitution of each AUG abolished the production of each corresponding polypeptide. Cell lines from individuals with the GC allele contain more B-type mRNAs than do those of GT homozygotes, and the former produce all of four polypeptides but the latter lack p26. Amounts of each polypeptide reflected copy number of the GC allele in each cell line. There is an apparent linkage disequilibrium between the two polymorphic sites, GT/GC at exon 2c and Val83/Met83 at codon 83 for p18.

本文言語英語
ページ(範囲)4335-4343
ページ数9
ジャーナルNucleic acids research
27
22
DOI
出版ステータス出版済み - 11 15 1999

All Science Journal Classification (ASJC) codes

  • 遺伝学

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