Tumor Biology

, Volume 33, Issue 1, pp 1–7 | Cite as

Inhibitor of growth-4 mediates chromatin modification and has a suppressive effect on tumorigenesis and innate immunity

Review

Abstract

Inhibitor of growth-4 (ING4) is a member of the ING family and acts as a tumor suppressor protein. ING4 is a promising candidate for cancer research due to its anti-angiogenic function and its role in the inhibition of cell migration, cell cycle, and induction of apoptosis. Interaction of this protein with the histone acetyl transferase complex plays a vital role in the regulation of multiple nuclear factor kappa light chain enhancer of activated B cells response elements and thus in the regulation of innate immunity. Splice variants of ING4 have different binding affinities to target sites, which results in the enhancement of its functional diversity. ING4 is among the few known regulatory proteins that can directly interact with chromatin as well as with transcription factors. The influence of ING4 on tumor necrosis factor-α, keratinocyte chemoattractant, interleukin (IL)-6, IL-8, matrix metalloproteinases, cyclooxygenase-2, and IκBα expression clearly demonstrates its critical role in the regulation of inflammatory mediators. Its interaction with liprin α1 and p53 contribute to mitigate cell spreading and induce apoptosis of cancer cells. Multiple factors including breast cancer melanoma suppressor-1 are upstream regulators of ING4 and are frequently deactivated in tumor cells. In the present review, the different properties of ING4 are discussed, and its activities are correlated with different aspects of cell physiology. Special emphasis is placed on our current understanding of ING4 with respect to its influence on chromatin modification, tumorigenesis, and innate immunity.

Keywords

Angiogenesis Histone acetylation Inflammation ING4 NF-κB Tumor 

Abbreviations

ALL

Adult acute lymphoblastic leukemia

BCR

B-cell receptor

BRMS1

Breast cancer melanoma suppressor-1

COX-2

Cyclooxygenase-2

EBV

Epstein–Barr virus

GFR

Growth factor receptor

H3K4me3

H3 trimethylated at position K4

HAT

Histone acetyl transferase

HBO1

HAT-associated ORC1

HDAC

Histone deacetylase

HIF

Hypoxia-inducible factor

HNSCC

Head and neck squamous cell carcinoma

HUVEC

Human umbilical vein endothelial cell

IL

Interleukin

ING4

Inhibitor of growth-4

KC

Keratinocyte chemoattractant

LAR

Leukocyte common antigen-related

MCP-1

Monocyte chemoattractant protein-1

MMP

Metalloproteinase

NF-κB

Nuclear factor kappa light chain enhancer of activated B cells

NLS

Nuclear localization sequence

PHD

Plant homeodomain

RANTES

Regulated upon activation normal T-cell expressed and secreted

ROS

Reactive oxygen species

RT-PCR

Reverse transcription polymerase chain reaction

TLR

Toll-like receptor

TNF

Tumor necrosis factor

Notes

Acknowledgment

This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1120340).

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  1. 1.Department of Microbiology and Immunology, School of MedicineJeju National UniversityJejuSouth Korea
  2. 2.Brain Korea 21 ProgramJeju National UniversityJejuSouth Korea

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