The Role of the E2F Transcription Factor Family in UV-Induced Apoptosis

Mehlika Hazar-Rethinam,Orla Gannon,Liliana Endo-Munoz,Nicholas Saunders

doi:10.3390/ijms12128947

Mehlika Hazar-Rethinam, Orla Gannon + Show 2 more

Open Access

https://doi.org/10.3390/ijms12128947

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Abstract

The E2F transcription factor family is traditionally associated with cell cycle control. However, recent data has shown that activating E2Fs (E2F1-3a) are potent activators of apoptosis. In contrast, the recently cloned inhibitory E2Fs (E2F7 and 8) appear to antagonize E2F-induced cell death. In this review we will discuss (i) the potential role of E2Fs in UV-induced cell death and (ii) the implications of this to the development of UV-induced cutaneous malignancies.

Highlights

The E2F transcription factor family is traditionally associated with cell cycle control
If the damage to DNA is perceived to be reparable, the keratinocytes will undergo a reversible growth arrest accompanied by the mobilisation and activation of the nucleotide excision repair system (NER)
The interplay between E2F1-stimulated apoptosis and E2F7/8-mediated inhibition of apoptosis is critical to understanding the role of E2Fs in UV-induced skin cancer formation and their potential as drugable targets for treating squamous cell carcinomas or enhancing chemotherapeutic responses

Summary

What is UV?

Life on earth is dependent upon UV radiation as an energy source. Ironically, whilst humans are dependent upon UV radiation for their existence, UV radiation is a common and potent carcinogen for people of Caucasian descent [1]. UVB (280–320 nm) radiation penetrates the atmosphere. UVA radiation predominates at sea level, UVB has the highest energy and is 1,000 times more erythematogenic than UVA [2]. The carcinogenic potential of the UV spectrum reaching the earth’s surface is a composite of a small amount of high energy UVB and a large amount of low energy UVA. UVA and UVB radiation damage DNA, disrupt pro-apoptotic signaling pathways and suppress immune responses contributing to the carcinogenic action of sunlight [3]. Despite the more potent carcinogenic activity of UVB it is only capable of penetrating the more superficial epidermal layers whereas UVA can penetrate deeper into the dermis [2]

Mutagenic Effects of UV Radiation

Role of UV in Skin Carcinogenesis

The E2F Family

E2F-Induced Apoptosis and Skin Cancer Formation