PDBsum entry 2m1r

Gene regulation

PDB id: 2m1r

Contents

Protein chain

63 a.a.

Metals

_ZN ×2

PDB id:

2m1r

Name:

Gene regulation

Title:

Phd domain of ing4 n214d mutant

Structure:

Inhibitor of growth protein 4. Chain: a. Synonym: p29ing4. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Variant: isoform 1. Gene: ing4, my036. Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

25 models

Authors:

F.J.Blanco

Key ref:

A.Moreno et al. (2010). Functional impact of cancer-associated mutations in the tumor suppressor protein ING4. Carcinogenesis, 31, 1932-1938. PubMed id: 20705953

Date:

05-Dec-12 Release date: 26-Dec-12

Protein chain

Q9UNL4  (ING4_HUMAN) -  Inhibitor of growth protein 4 from Homo sapiens

Seq: 249 a.a.

Struc: 63 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

Carcinogenesis 31:1932-1938 (2010)

PubMed id: 20705953

Functional impact of cancer-associated mutations in the tumor suppressor protein ING4.

A.Moreno, A.Palacios, J.L.Orgaz, B.Jimenez, F.J.Blanco, I.Palmero.

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.