Methylosome Protein 50 and PKCδ/p38δ Protein Signaling Control Keratinocyte Proliferation via Opposing Effects on p21Cip1 Gene Expression

Saha, Kamalika; Eckert, Richard L.

doi:10.1074/jbc.m115.642868

Cited by 13 publications

(14 citation statements)

References 49 publications

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“…In the nucleus, PRMT5 has been reported to promote cell proliferation and transformation via the switch/sucrose non‐fermenting (SWI/SNF) complex and nucleosome remodeling deacetylase (NuRD) chromatin‐remodeling complexes, in which it may methylate histones as well as transcription factors or regulators . In the cytoplasm, PRMT5 forms a 20S protein arginine methyltransferase complex termed the “methylosome”, which consists of spliceosomal snRNP Sm proteins, PRMT5, pICIn, and MEP50, to function as a master regulator of splicing …”

Section: Discussionmentioning

confidence: 99%

Expression of protein arginine methyltransferase‐5 in oral squamous cell carcinoma and its significance in epithelial‐to‐mesenchymal transition

Amano

Matsubara

Yoshimoto

et al. 2018

Pathology International

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Protein arginine methyltransferases (PRMT) 5, a member of type II arginine methyltransferases, catalyzes the symmetrical dimethylation of arginine residues on histone and non-histone substrates. Although the overexpression of PRMT5 has been reported in various cancers, its role in oral squamous cell carcinoma (OSCC) has not been elucidated. In the present study, we immunohistochemically examined the expression of PRMT5 in surgically resected oral epithelial dysplasia (OED, n = 8), oral intraepithelial neoplasia (OIN)/carcinoma in situ (CIS) (n = 11) and OSCC (n = 52) with or without contiguous OED lesions. In the normal epithelium, PRMT5 was weakly expressed in the cytoplasm of basal layer cells. In OED, OIN/CIS, and OSCC, its expression consistently and uniformly increased in the cytoplasm of dysplastic and cancer cells. Moreover, nuclear and cytoplasmic localization was detected in the invasive front of cancer cells, particularly in cases showing poor differentiation or aggressive invasion patterns. The concomitant nuclear and cytoplasmic expression of PRMT5 correlated with the loss of E-cadherin and cytokeratin 17, and the upregulation of vimentin, features that are both indicative of epithelial-to-mesenchymal transition. PRMT5 may play a role from early oncogenesis through to the progression of OSCC, particularly in the aggressive mode of stromal invasion.

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Section: Discussionmentioning

confidence: 99%

Expression of protein arginine methyltransferase‐5 in oral squamous cell carcinoma and its significance in epithelial‐to‐mesenchymal transition

Amano

Matsubara

Yoshimoto

et al. 2018

Pathology International

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“…MAPK kinases have long been implicated in keratinocyte differentiation; several MAP kinases, Mapk3, Mapk13 and Mapk14, are specifically expressed in the upper epidermis in the mouse on the mRNA level and knockouts of Mapk13 and murine models with modulation of MAPK signalling pathways display barrier defects, implicating these kinases in epidermal terminal differentiation . Additionally, the Erk1/2 effector c‐Jun is phosphorylated in the granular layer, in vitro and in vivo , suggesting that Erk1/2 is active in this region .…”

Section: Kinase Expression In the Upper Epidermismentioning

confidence: 99%

“…Induces p21 and epidermal terminal differentiation [49] MAPK14 ✓ Mitogen-activated protein kinase 14…”

Section: Erk/mapk/jnk Kinasesmentioning

confidence: 99%

“…[46] MAPK kinases have long been implicated in keratinocyte differentiation [47] ; several MAP kinases, Mapk3, Mapk13 and Mapk14, are specifically expressed in the upper epidermis in the mouse on the mRNA level [24] and knockouts of Mapk13 and murine models with modulation of MAPK signalling pathways display barrier defects, implicating these kinases in epidermal terminal differentiation. [48][49][50] Additionally, the Erk1/2 effector c-Jun is phosphorylated in the granular layer, in vitro and in vivo, suggesting that Erk1/2 is active in this region. [51][52][53] More recent work in human epidermis indicates a gradient of MAPK and ERK activation across the differentiating epidermis, correlating with the calcium gradient, [54,55] with ERK1/2 active in the nucleus of granular layer keratinocytes further suggesting a role for this signalling pathway in keratinocyte differentiation.…”

Section: Erk/mapk/jnk Kinasesmentioning

confidence: 99%

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Protein kinases involved in epidermal barrier formation: The AKT family and other animals

Rogerson

O'Shaughnessy

2018

Experimental Dermatology

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Formation of a stratified epidermis is required for the performance of the essential functions of the skin; to act as an outside-in barrier against the access of microorganisms and other external factors, to prevent loss of water and solutes via inside-out barrier functions and to withstand mechanical stresses. Epidermal barrier function is initiated during embryonic development and is then maintained throughout life and restored after injury. A variety of interrelated processes are required for the formation of a stratified epidermis, and how these processes are both temporally and spatially regulated has long been an aspect of dermatological research. In this review, we describe the roles of multiple protein kinases in the regulation of processes required for epidermal barrier formation.

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“…The in vitro keratinocytes culture system have been successfully developed and used for many years to mimic normal skin formation . Though the current 3D reconstructed system, as a completed epidermis‐like structure, has been mainly used for tests or diagnoses in place of human epidermis, it is also appropriate for studies on keratinocyte differentiation . So far, the mechanisms of CE formation in terminal differentiation have been biochemically characterized regarding properties, components, and modification by TGs in the skin epidermis and ordinary 2D cultured cells .…”

Section: Discussionmentioning

confidence: 99%

Studies on differentiation‐dependent expression and activity of distinct transglutaminases by specific substrate peptides using three‐dimensional reconstituted epidermis

et al. 2019

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During skin formation, particularly during differentiation of keratinocytes, unique post‐translational modifications play a role in forming a proteinaceous supermolecule called the cornified envelope (CE), which is necessary for barrier function. Transglutaminases (TGs) are essential enzymes involved in the cross‐linking of various keratinocyte structural proteins to complete CE formation. The TG family consists of eight isozymes, with two members, TG1 and TG3, located mainly in the epidermis. In an in vitro three‐dimensional (3D) culture system, reconstruction of the epidermis allows cornification of the terminally differentiated keratinocytes. In this study, using isozyme‐specific substrate peptides that enable detection of TG activity, we investigated the expression and the activation pattern of each isozyme during differentiation in this culture system. In the differentiating cells, the protein levels, enzymatic activities, as well as localization of TG1 and TG3 exhibited distinct patterns. Specific knockdown of these enzymes by siRNA revealed less cornification, suggesting that each TG contributes to the epidermal formation. In conclusion, we demonstrate the efficiency of the 3D system for studying differentiation‐dependent expression and activity of distinct TGs by specific substrate peptides. Enzyme Transglutaminase, http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/3/2/13.html.

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Methylosome Protein 50 and PKCδ/p38δ Protein Signaling Control Keratinocyte Proliferation via Opposing Effects on p21Cip1 Gene Expression

Cited by 13 publications

References 49 publications

Expression of protein arginine methyltransferase‐5 in oral squamous cell carcinoma and its significance in epithelial‐to‐mesenchymal transition

Expression of protein arginine methyltransferase‐5 in oral squamous cell carcinoma and its significance in epithelial‐to‐mesenchymal transition

Protein kinases involved in epidermal barrier formation: The AKT family and other animals

Studies on differentiation‐dependent expression and activity of distinct transglutaminases by specific substrate peptides using three‐dimensional reconstituted epidermis

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