Expression, regulation, and function of the SPR family of proteins

Abstract

The small, proline-rich (SPR) genes consist of three subclasses closely linked on human chromosome 1, a region referred to as the epidermal differentiation complex. SPR genes consist of two exons, with the second exon containing the entire open reading frame. SPRs are expressed in all squamous tissues of the skin, scalp, footpad, vaginal epithelia, and most of the epithelial lining of the digestive tract, including the lip, tongue, esophagus, and forestomach. Although SPR1 is absent in normal mucociliary epithelium of the respiratory tract, epithelia that undergo squamous differentiation in response to vitamin-A deficiency or to injury owing to exposure to environmental toxicants express SPR1. High levels of SPR1 are detected in various diseases and cancers of the skin or respiratory epithelia and in nonkeratinizing papillary adenocarcinomas. SPR expression can be regulated by transcriptional factors, by posttranscriptional factors, or by factors that affect SPR1 mRNA translation or protein turnover. Furthermore, regulation can be affected by the state of cell proliferation. The presence of SPR1 in most of these epithelia, and the absence of SPR3 in normal skin, suggest that these subclasses have distinct functions. Various approaches to the study of the cross-linked envelope (CE) components in identifying SPR1 and SPR2 and in suggesting that SPRs are one of the precursor proteins of the CE. However, expression of SPR1 in nonsquamous tissues and cell lines indicates a function not associated with squamous differentiation. Several studies have demonstrated that SPR1 antibodies react with nuclear proteins and that SPR1 is expressed in cells before entering the G0 phase of the cell cycle. Future studies should clarify the role of SPRs by modifying their contents in CE, and should identify SPR-associated proteins to clarify the cell growth-related role of SPR1.

Gene expression pattern and hormonal regulation of Small Proline-Rich Protein 2 family members in the female mouse reproductive system during the estrous cycle and pregnancy

“…It was reported that the SPRR1 protein played a role in the nucleus and was associated with G0 entering of the cell cycle, and SPRR2 expression was reversely related to the proliferation state in the keratinocyte, partially due to the activation of p27, p21 and p16 Ink4α [24][25][26][27]. Under the effects of cycling steroid hormones, uterine luminal and glandular epithelial cells have higher mitotic rates at the diestrous and proestrous stages, and undergo apoptosis at the estrous and metestrous stages [28].…”

Suppressive Effect of IL-4 on IL-13-Induced Genes in Mouse Lung

“…The products of these genes contribute to the cellular envelope of squamous epithelial cells, which decreases epithelial permeability and perhaps increases epithelial rigidity (64,65). In addition, SPRR proteins have been reported to migrate to the nucleus and influence gene expression and cellular differentiation (66). Both of these effects may influence airway responsiveness, and the latter effect has the potential to influence goblet cell differentiation and mucus production.…”

Bmx Tyrosine Kinase Transgene Induces Skin Hyperplasia, Inflammatory Angiogenesis, and Accelerated Wound Healing

“…The up-regulated genes included also stromelysin-1/ matrix metalloproteinase-3 (MMP-3), a proteinase with strong involvement in tumor development (Sternlicht et al, 2000) and the serine protease BSSP, which is robustly induced in the skin by treatment with the tumor promoter phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA; Breitenbach et al, 2001). Furthermore, transcripts for keratin 6 and keratin 16, which are associated with epithelial hyperproliferation as well as for small proline-rich proteins (Sprr) associated with keratinocyte differentiation and epithelial barrier function (Tesfaigzi and Carlson, 1999;Chu and Weiss, 2002) were up-regulated.…”