Disease relevance of SPRR1B

• SPRR1B expression was downregulated in the cell lines derived from adenocarcinoma when cells were enriched in G0 at low confluence [1].
• Northern blot analysis revealed that cornifin-alpha mRNA was present in all the squamous epithelial tissues studied, whereas cornifin-beta mRNA was expressed in oral mucosal epithelia and verrucous carcinoma of the skin but neither in normal nor in psoriatic skin [2].
• SPRR1B expression is either detectable or PMA (phorbol 13-myristate 12-acetate) -inducible in several malignant BE cells including squamous, adeno, small and large cell carcinomas [3].
• We conclude that SPRR is expressed in close association with epidermal differentiation in normal skin and skin diseases [4].
• In epidermolytic hyperkeratosis, degenerated squamous cells widely expressed SPRR [4].

High impact information on SPRR1B

• Cornifin, a cross-linked envelope precursor in keratinocytes that is down-regulated by retinoids [5].
• The protein, which has been named cornifin, has a high content of proline (31%), glutamine (20%), and cysteine (11%) and contains 13 repeats of an octapeptide (consensus sequence, EPCQPKVP) at its C terminus [5].
• Overexpression of SPRR1B in bronchial epithelial cells is a marker for early metaplastic changes induced by various toxicants/carcinogens [6].
• Furthermore, preceding SPRR1B transcription, PMA up-regulated mRNA expression of ETS family members such as ESE-1 and ESE-3 [6].
• Consistent with this, overexpression of EBS-binding proteins ESE-1 and ESE-3 significantly stimulated SPRR1B promoter activity [6].

Chemical compound and disease context of SPRR1B

• Expression of SPRR1B was detected by Northern blotting in a higher percentage of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced compared with beryllium metal-induced rat lung adenocarcinomas [1].
• Decreased expression of retinoic acid receptors, transforming growth factor beta, involucrin, and cornifin in cervical intraepithelial neoplasia [7].

Biological context of SPRR1B

• SPRR1B overexpression enhances entry of cells into the G0 phase of the cell cycle [1].
• We reported that expression of SPRR1B in Chinese hamster ovary (CHO) cells is increased as they enter the G0 phase of the cell cycle [1].
• These findings indicate that SPRR1B is likely coupled primarily to signals responsible for withdrawal from the proliferative state rather than the final stages of cellular quiescence and that its overexpression for prolonged periods may disrupt the normal progression of mitosis [1].
• Tetraploidy was induced in CHO, mouse, and human tumor cell lines by stably overexpressing SPRR1B, whereas control cells showed no change in ploidy [1].
• All SPRR genes are closely linked within a 300-kb DNA segment on human chromosome 1 band q21-q22, a region where the related loricrin and involucrin genes have also been mapped [8].

Anatomical context of SPRR1B

• Various toxicants and carcinogens upregulate the expression of small proline-rich protein 1B (SPRR1B), a squamous differentiation marker, in bronchial epithelial cells both in vivo and in vitro [9].
• In normal human skin, cornifin-alpha was expressed in the granular layer of the epidermis of palmoplantar skin, in the inner lining cells of the follicular infundibulum, and in the inner root sheath of the hair follicle [2].
• Molecular characterization and evolution of the SPRR family of keratinocyte differentiation markers encoding small proline-rich proteins [8].
• The overexpression of SPRR1B in bronchial epithelium is a marker for early metaplastic changes and the loss of its expression is associated with an irreversible malignant transformation [3].
• It is highly expressed in esophagus, tongue, and oral mucosa but, in contrast to cornifin alpha, is not detectable in the epidermis [10].

Associations of SPRR1B with chemical compounds

• Cloning and regulation of cornifin beta, a new member of the cornifin/spr family. Suppression by retinoic acid receptor-selective retinoids [10].
• Both retinoic acid and a retinoid selective for the nuclear retinoic acid receptors were very potent suppressors of cornifin beta expression while an analog selective for the nuclear retinoid X receptors was much less effective, suggesting that a specific retinoid signaling pathway is involved in this suppression [10].
• The expressed protein contains multiple direct repeats of an 8-amino acid motif rich in proline, with significant homology to the cornifin, pig 20K, monkey MT5, and human small proline-rich genes spri and spril [11].
• Cornifin mRNA and protein, which are absent in the normal mucociliary tracheal epithelium, are induced in the suprabasal layers of the squamous metaplastic tracheal epithelium of vitamin A-deficient hamsters [12].
• Using a protein kinase (PK) C inhibitor, bisindolylmaleimide I, PMA-induced cell cornification and SPRR1 gene expression were abolished [13].

Physical interactions of SPRR1B

• Intriguingly, the composition of AP-1 protein binding to the -152 to -86 bp SPRR1B promoter is quite different [3].

Regulatory relationships of SPRR1B

• BMK1 (ERK5) regulates squamous differentiation marker SPRR1B transcription in Clara-like H441 cells [9].
• Overexpression of fra1 in malignant cells significantly enhanced SPRR1B promoter activity [3].

Other interactions of SPRR1B

• Here we show that SPRR proteins are encoded by closely related members of a gene family, consisting of two genes of SPRR1, approximately seven genes for SPRR2, and a single gene for SPRR3 [8].
• The transcriptional induction of SPRR1B by phorbol 12-myristate 13-acetate (PMA) is mainly mediated by the first -152-base pair 5'-flanking region containing two functional AP-1 sites [14].
• In the distal SPRR1A promoter region, a complex arrangement of positive and negative regulatory elements, which are only conditionally needed for promoter activity, are likely involved in gene-specific fine-tuning of the expression of this member of the SPRR gene family [15].
• In untreated cells, SPRR1B promoter is predominantly occupied by JunD and Fra2 [3].
• This conclusion is further substantiated by the finding that expression of ESE-1, an Ets transcription factor involved in SPRR regulation, is also induced by TPA, with kinetics similar to SPRR1A [15].

Analytical, diagnostic and therapeutic context of SPRR1B

• In situ hybridizations confirmed that SPRR1B is expressed in individual or clusters of cells of nonsquamous cells from mouse, rat, and human adenocarcinomas [1].
• By deletion and site-directed mutagenesis, two distinct roles of the amino- and carboxyl-terminal sequences of SPRR1 have been demonstrated [16].

References