Galectin-3 Protects Keratinocytes from UVB-Induced Apoptosis by Enhancing AKT Activation and Suppressing ERK Activation

Saegusa, Jun; Hsu, Daniel K.; Liu, Wei; Kuwabara, Ichiro; Kuwabara, Yasuko; Yu, Liang; Liu, Fu‐Tong

doi:10.1038/jid.2008.119

Cited by 46 publications

(37 citation statements)

References 51 publications

(60 reference statements)

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“…These data suggested that the MAPK or caspase-3/Mst1 pathways may have some, as yet unknown, functional involvement in the regulation of H2B phosphorylation. As reported previously, MAPKs (ERK1/2, JNK1/2, p38) are involved in UV-induced activation of caspase-3 and apoptosis [21][22][23]. Hence we investigated whether UVBtriggered MAPKs regulate H2B phosphorylation (Figure 2) via the caspase-3/Mst1 pathway.…”

Section: Uvb-activated Mst1/caspase-3 and Mapk Pathways Regulate H2b mentioning

confidence: 93%

MAPKs and Mst1/Caspase-3 pathways contribute to H2B phosphorylation during UVB-induced apoptosis

Shi

Luo

et al. 2010

Sci. China Life Sci.

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Apoptosis is a highly coordinated or programmed cell suicide mechanism in eukaryotes. Histone modification is associated with nuclear events in apoptotic cells. Specifically H2B phosphorylation at serine 14 (Ser14) catalyzed by Mst1 kinase has been linked to chromatin condensation during apoptosis. We report that activation of MAPKs (ERK1/2, JNK1/2 and p38) together with Mst1 and caspase-3 is required for phosphorylation of H2B (Ser14) during ultraviolet B light (UVB)-induced apoptosis. UVB can trigger activation of MAPKs and induce H2B phosphorylation at Ser14 but not acetylation in a time-dependent manner. Inhibition of ERK1/2, JNK1/2 or p38 activity blocked H2B phosphorylation (Ser14). Furthermore, caspase-3 was activated by UVB to regulate Mst1 activity, which phosphorylates H2B at Ser14, leading to chromatin condensation. Full inhibition of caspase-3 activity reduced Mst1 activation and partially inhibited H2B phosphorylation (Ser14), but ERK1/2, JNK1/2 and p38 activities were not affected. Taken together, these data revealed that H2B phosphorylation is regulated by both MAPKs and caspase-3/Mst1 pathways during UVB-induced apoptosis.

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Section: Uvb-activated Mst1/caspase-3 and Mapk Pathways Regulate H2b mentioning

confidence: 93%

MAPKs and Mst1/Caspase-3 pathways contribute to H2B phosphorylation during UVB-induced apoptosis

Shi

Luo

et al. 2010

Sci. China Life Sci.

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“…It was recently shown that galectin-3, a member of a family of beta-galactoside-binding animal lectins expressed abundantly in keratinocytes and other epithelial cells, protects keratinocytes from apoptosis induced by UVB or by various other stimuli, both in vitro and in vivo [64]. Moreover, it was demonstrated that the increased apoptosis in gal3 -/-keratinocytes is attributable to lower AKT activation after UVB irradiation.…”

Section: Ikkbmentioning

confidence: 97%

Cell death in the skin

et al. 2009

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The skin is the largest organ of the body and protects the organism against external physical, chemical and biological insults, such as wounding, ultraviolet radiation and micro-organisms. The epidermis is the upper part of the skin that is continuously renewed. The keratinocytes are the major cell type in the epidermis and undergo a specialized form of programmed cell death, called cornification, which is different from classical apoptosis. In keep with this view, several lines of evidence indicate that NF-kB is an important factor providing protection against keratinocyte apoptosis in homeostatic and inflammatory conditions. In contrast, the hair follicle is an epidermal appendage that shows cyclic apoptosis-driven involution, as part of the normal hair cycle. The different cell death programs need to be well orchestrated to maintain skin homeostasis. One of the major environmental insults to the skin is UVB radiation, causing the occurrence of apoptotic sunburn cells. Deregulation of cell death mechanisms in the skin can lead to diseases such as cancer, necrolysis and graft-versus-host disease. Here we review the apoptotic and the anti-apoptotic mechanisms in skin homeostasis and disease.

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“…The increase in apoptosis was attributed to an increase in ERK and c-Jun N-terminal kinase (JNK), but a decrease in AKT activation after UVB irradiation. Thus, galectin-3 may play a role in other apoptosis-related responses of keratinocytes through suppressing ERK activation and enhancing AKT activation (Saegusa et al, 2008). Recombinant galectin-3 has been shown to induce keratinocyte migration possibly through an extracellular interaction with beta4 integrin, EGFR, and laminin on the keratinocyte matrix (Kariya et al, 2010).…”

Section: Role Of Galectin-3 In the Biological Responses Of Skin Cellsmentioning

confidence: 99%

Galectin-3 and the skin

Larsen

Chen

Saegusa

et al. 2011

Journal of Dermatological Science

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Galectin-3 is highly expressed in epithelial cells including keratinocytes and is involved in the pathogenesis of inflammatory skin diseases by affecting the functions of immune cells. For example, galectin-3 can contribute to atopic dermatitis (AD) by promoting polarization toward a Th2 immune response by regulating dendritic cell (DC) and T cell functions. In addition, galectin-3 may be involved in the development of contact hypersensitivity by regulating the migratory capacity of antigen presenting cells. Galectin-3 may act as a regulator of epithelial tumor progression and development through various signaling pathways, such as inhibiting keratinocyte apoptosis through regulation of the activation status of extracellular signal-regulated kinase (ERK) and activated protein kinase B (AKT). Galectin-3 is detected at different stages of melanoma development. In contrast, a marked decrease in the expression of galectin-3 is observed in non-melanoma skin cancers, such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Galectin-3 may play an important role in tumor cell growth, apoptosis, cell motility, invasion, and metastasis. Galectin-3 may be a novel therapeutic target for a variety of skin diseases.

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Galectin-3 Protects Keratinocytes from UVB-Induced Apoptosis by Enhancing AKT Activation and Suppressing ERK Activation

Cited by 46 publications

References 51 publications

MAPKs and Mst1/Caspase-3 pathways contribute to H2B phosphorylation during UVB-induced apoptosis

MAPKs and Mst1/Caspase-3 pathways contribute to H2B phosphorylation during UVB-induced apoptosis

Cell death in the skin

Galectin-3 and the skin

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