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Absent in melanoma 2 proteins in the development of cancer

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Abstract

Recent studies utilizing chemical-induced colitis-associated and sporadic colon cancer in mouse models indicated a protective role for absent in melanoma 2 (Aim2) in colon epithelial cells. Accordingly, mutations in the human AIM2 gene have been found in colorectal cancer (CRC), and reduced expression of AIM2 in CRC is associated with its progression. Furthermore, the overexpression of AIM2 protein in human cancer cell lines inhibits cell proliferation. Interferon-inducible Aim2 and AIM2 are members of the PYHIN (PYRIN and HIN domain-containing) protein family and share ~57 % amino acid identity. The family also includes murine p202, human PYRIN-only protein 3, and IFI16, which negatively regulate Aim2/AIM2 functions. Because the CRC incidence and mortality rates are higher among men compared with women and the expression of Aim2/AIM2 proteins and their regulators is dependent upon age, gender, and sex hormones, we discuss the potential roles of Aim2/AIM2 in the development of cancer. An improved understanding of the biological functions of the AIM2 in the development of CRC will likely identify new therapeutic approaches to treat patients.

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Abbreviations

Aim2:

Absent in melanoma 2 (murine)

AIM2:

Absent in melanoma 2 (human)

AR:

Androgen receptor

ASC:

Apoptotic speck protein containing a caspase recruitment domain

ATM:

Ataxia telangiectasia

BMDM:

Bone marrow-derived macrophage

CAC:

Colitis-associated cancer

CRC:

Colorectal cancer

DHT:

Dihydrotestosterone

ERα:

Estrogen receptor-α

IFN:

Interferon

ISGs:

Interferon-stimulated genes

POP3:

PYRIN-only protein 3

PrECs:

Prostate epithelial cells

PYD:

PYRIN domain

PYHIN:

YRIN and HIN domain-containing

TMA:

Tissue microarray

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Acknowledgments

Research work in author’s laboratory was supported by a Merit Award (I01BX001133) from the Veterans Administration (VA). The author apologizes to those colleagues, whose research work could not be cited directly due to space limitations.

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  1. Research Service, Cincinnati VA Medical Center, 3200 Vine Street, ML-151, Cincinnati, OH, 45220, USA

    Divaker Choubey

  2. Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, P. O. Box-670056, Cincinnati, OH, 45267, USA

    Divaker Choubey

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Choubey, D. Absent in melanoma 2 proteins in the development of cancer. Cell. Mol. Life Sci. 73, 4383–4395 (2016). https://doi.org/10.1007/s00018-016-2296-9

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