2M1R

PHD domain of ING4 N214D mutant

2M1R の概要

• エントリーDOI: 10.2210/pdb2m1r/pdb
• 関連するPDBエントリー: 1PNX 2k1J 2VNF 4AFL
• NMR情報: BMRB: 18874
• 分子名称: Inhibitor of growth protein 4, ZINC ION (2 entities in total)
• 機能のキーワード: ing4, phd, transcription, gene regulation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9UNL4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7457.28

構造登録者

Blanco, F.J. (登録日: 2012-12-05, 公開日: 2012-12-26, 最終更新日: 2024-05-01)

主引用文献

Moreno, A.,Palacios, A.,Orgaz, J.L.,Jimenez, B.,Blanco, F.J.,Palmero, I.
Functional impact of cancer-associated mutations in the tumor suppressor protein ING4.
Carcinogenesis, 31:1932-1938, 2010

PubMed Abstract: Inhibitor of growth 4 (ING4) is a member of the ING family of tumor suppressor proteins. In this study, we have analyzed the impact of two mutations in ING4 associated with human tumors (Y121N and N214D), testing their behavior in a series of functional, biochemical and structural analyses. We report that the N214D mutation dramatically dampened the ability of ING4 to inhibit proliferation, anchorage-independent growth or cell migration or to sensitize to cell death. In turn, the Y121N mutant did not differ significantly from wild-type ING4 in our assays. Neither of the mutations altered the normal subcellular localization of ING4, showing predominantly nuclear accumulation. We investigated the molecular basis of the defect in the activity of the N214D mutant. The folding and ability to bind histone marks of ING4 was not significantly altered by this mutation. Instead, we found that the functional impairment of the N214D mutant correlates with reduced protein stability due to increased proteasome-mediated degradation. In summary, our data demonstrates that a point mutation of ING4 associated to human tumors leads to the loss of several essential functions of ING4 pertinent to tumor protection and highlight the importance of ING4 function to prevent tumorigenesis.

PubMed: 20705953
DOI: 10.1093/carcin/bgq171

実験手法

SOLUTION NMR