Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tumour suppressor gene p53 encodes a phosphoprotein involved in the control of cell growth. It's expression and function have been documented in malignancy, apoptosis and the aging processes. Recently, p53 expression has been demonstrated in normal murine tissues, including whole eye. Currently, we intend to map and to characterize p53 expression in the normal cornea across different species. To do this, eyes of animals were enucleated after sacrifice by CO(2) narcosis and then p53 expression in whole eyes (cornea) was mapped by indirect immunohistochemical staining techniques using the anti-p53 monoclonal antibodies PAb 248, PAb 421 and PAb 240 (alternatively called mAb 248, mAb 421 and mAb 240, respectively). Additionally, eyes were freshly dissected to separate the corneas, for quantitating p53 expression, using Western blot analysis. We found strong cytoplasmic p53 expression in the corneal epithelium of various vertebrate species by immunohistochemistry and by Western analysis. High levels of cytoplasmic p53 protein were normally found in normal corneal epithelium of various vertebrate species. Hence, these data may indicate that p53 may have a new evolutionary significant function in the eye.
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PMID:Identification of cytoplasmic p53 protein in corneal epithelium of vertebrates. 1637 31

Ultraviolet radiation (UV) from sunlight is the primary cause of skin and ocular neoplasia. Brahma (BRM) is part of the SWI/SNF chromatin remodeling complex. It provides energy for rearrangement of chromatin structure. Previously we have found that human skin tumours have a hotspot mutation in BRM and that protein levels are substantially reduced. Brm-/- mice have enhanced susceptibility to photocarcinogenesis. In these experiments, Brm-/- mice, with both or a single Trp53 allele were exposed to UV for 2 or 25 weeks. In wild type mice the central cornea and stroma became atrophic with increasing time of exposure while the peripheral regions became hyperplastic, presumably as a reparative process. Brm-/-, Trp53+/-, and particularly the Brm-/- Trp53+/- mice had an exaggerated hyperplastic regeneration response in the corneal epithelium and stroma so that the central epithelial atrophy or stromal loss was reduced. UV induced hyperplasia of the epidermis and corneal epithelium, with an increase in the number of dividing cells as determined by Ki-67 expression. This response was considerably greater in both the Brm-/- Trp53+/+ and Brm-/- Trp53+/- mice indicating that Brm protects from UV-induced enhancement of cell division, even with loss of one Trp53 allele. Cell division was disorganized in Brm-/- mice. Rather than being restricted to the basement membrane region, dividing cells were also present in the suprabasal regions of both tissues. Brm appears to be a tumour suppressor gene that protects from skin and ocular photocarcinogenesis. These studies indicate that Brm protects from UV-induced hyperplastic growth in both cutaneous and corneal keratinocytes, which may contribute to the ability of Brm to protect from photocarcinogenesis.
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PMID:Brm inhibits the proliferative response of keratinocytes and corneal epithelial cells to ultraviolet radiation-induced damage. 2525 62