DAD1

Official Full Name

defender against cell death 1

Organism

Homo sapiens

GeneID

1603

Background

DAD1, the defender against apoptotic cell death, was initially identified as a negative regulator of programmed cell death in the temperature sensitive tsBN7 cell line. The DAD1 protein disappeared in temperature-sensitive cells following a shift to the nonpermissive temperature, suggesting that loss of the DAD1 protein triggered apoptosis. DAD1 is believed to be a tightly associated subunit of oligosaccharyltransferase both in the intact membrane and in the purified enzyme, thus reflecting the essential nature of N-linked glycosylation in eukaryotes. [provided by RefSeq, Jul 2008]

Synonyms

OST2;

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Detailed Information

Defender Against Cell Death 1 (DAD1) is a pivotal protein involved in crucial cellular processes, ranging from apoptosis regulation to protein glycosylation.

Structural Features of DAD1

DAD1 is a highly conserved protein characterized by its unique topology. It possesses transmembrane domains that anchor it within the endoplasmic reticulum (ER) membrane. Additionally, DAD1 interacts with other proteins, forming complexes essential for its diverse functions. The DAD1 gene is a crucial regulator of development, encoding a protein that plays a significant role in the regulation of cell division and differentiation. Its structure is highly conserved across various species. The gene is composed of several exons and introns, which encode a protein with multiple functional domains. These domains include a DNA binding domain, a transcription activation domain, and a protein interaction domain.

DAD1 Is Involved in Apoptosis

The DAD1 gene is a crucial regulator in the process of apoptosis, which is the programmed cell death necessary for maintaining tissue homeostasis and development. Research indicates that DAD1 functions as an inhibitor of cell death, preventing unnecessary cell loss in various physiological contexts.

The expression of DAD1 occurs during periods of cell stress or upon exposure to apoptotic signals. Upon activation, this gene promotes the synthesis of its protein product, which interacts with key signaling molecules to interfere with the initiation of apoptosis. Specifically, DAD1 has been shown to inhibit the activation of caspase enzymes, which are responsible for cleaving cellular proteins and leading to cell death.

Inhibition of caspase activity by DAD1 results in the prevention of DNA fragmentation, cell membrane shrinkage, and other hallmarks of apoptosis. This process allows cells to recover from potential threats to their survival and maintain their functional integrity. However, unchecked DAD1 expression can also lead to abnormal cell survival, contributing to the development of diseases such as cancer.

Figure1. Feasible interaction between BAD and DAD1 and sequential apoptosis.

DAD1 And Cancer

The DAD1 gene has been implicated in the development and progression of cancer, as its role in regulating cell survival and apoptosis makes it a crucial player in the balance of cellular processes. In normal cells, DAD1 functions as an inhibitor of cell death, protecting cells from unnecessary loss. However, in cancer cells, dysregulated DAD1 expression can lead to unchecked cell survival and proliferation, contributing to the formation and spread of tumors. Increased expression of DAD1 has been associated with more aggressive tumor growth and a worse prognosis for patients. The mechanism by which DAD1 contributes to cancer development is complex and still under investigation. Research suggests that DAD1 may promote cancer cell survival by inhibiting apoptosis, DNA repair, and cell cycle arrest. Additionally, DAD1 has been shown to enhance the invasion and metastasis of cancer cells, further contributing to the progression of the disease. As a result, targeting the DAD1 gene has emerged as a potential strategy for cancer treatment and prevention. Research into DAD1 inhibitors is ongoing, with some studies demonstrating promising results in laboratory and animal models. These inhibitors aim to restore the normal balance of cell survival and death, thereby preventing the unchecked growth and spread of cancer cells.

References:

Kelleher DJ, Gilmore R. DAD1, the defender against apoptotic cell death, is a subunit of the mammalian oligosaccharyltransferase. Proc Natl Acad Sci U S A. 1997 May 13;94(10):4994-9. doi: 10.1073/pnas.94.10.4994. PMID: 9144178; PMCID: PMC24619.
Pires AO, Queiroz GA, de Jesus Silva M, da Silva RR, da Silva HBF, Carneiro NVQ, Fonseca HF, de Santana MBR, Nascimento RS, Alcântara-Neves NM, Costa GNO, Costa RDS, Barreto ML, Figueiredo CA. Polymorphisms in the DAD1 and OXA1L genes are associated with asthma and atopy in a South American population. Mol Immunol. 2018 Sep;101:294-302. doi: 10.1016/j.molimm.2018.07.014. Epub 2018 Jul 19. PMID: 30032071.
Halberda JP, Middaugh LD, Gard BE, Jackson BP. DAD1- and DAD2-like agonist effects on motor activity of C57 mice: differences compared to rats. Synapse. 1997 May;26(1):81-92. doi: 10.1002/(SICI)1098-2396(199705)26:1<81::aid-syn9>3.0.CO;2-A. PMID: 9097408.

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