Disease relevance of SPRR2A

• This first report of expression of ESE-1, and of SPRR2A and ENDOA/CK8 (both related to terminal differentiation in different types of epithelia lining) in anal cancer excludes the hypothesis that these genes influenced carcinogenesis in our patients [1].
• The metabolism of hydroxyproline was investigated in six healthy subjects and four patients with chronic renal insufficiency (creatinine clearances respectively 40, 10, 7, 2 1/2 ml/min) [2].

High impact information on SPRR2A

• Interdependent transcription control elements regulate the expression of the SPRR2A gene during keratinocyte terminal differentiation [3].
• Skn-1a and Skn-1d1 bound the SPRR2A octamer site with comparable affinity and functioned as transcriptional activators [4].
• The strict AP-1 requirement in SPRR1A for calcium-induced differentiation is not found for SPRR2A, despite the presence of an identical AP-1 consensus binding site in this gene [5].
• Interestingly, ELF3 suppressed basal keratin 4 promoter activity in both esophageal and cervical epithelial cancer cell lines, a novel result, while simultaneously activating the late-differentiation linked SPRR2A promoter [6].
• Apparently, the association of the SPRR2A gene with the nuclear matrix results in a general, differentiation-independent enhancement of gene expression [7].

Biological context of SPRR2A

• The single intron of SPRR2A enhanced the activity of the SPRR2A promoter in transient transfection assays [7].
• The inhibitory effect is targeted to a 150-bp minimal promoter region, which is essential and sufficient for SPRR2A expression during keratinocyte terminal differentiation [8].
• The conserved high mobility group (HMG) box domain found in the MAT1-2-1 protein was used as a starting point for cloning and sequencing the entire MAT1-2 idiomorph plus flanking regions [9].

Anatomical context of SPRR2A

• CONCLUSIONS: The up-regulated expression of keratin 6 and -16, small proline-rich protein 2A, and kallikrein 7 in the conjunctival epithelium of SS patients suggests an anomalous keratinization pattern [10].

Associations of SPRR2A with chemical compounds

• Expression of the SPRR2A gene, a member of the small proline-rich family of cornified cell envelope precursor proteins, is strictly linked to keratinocyte terminal differentiation both in vivo and in vitro [3].

Regulatory relationships of SPRR2A

• Epidermal growth factor (EGF) enhances the expression of the keratinocyte terminal differentiation marker SPRR2A, when added to monolayers of basal keratinocytes, induced to stratify by increasing the extracellular calcium concentration [8].

Other interactions of SPRR2A

• This indicates that the Ras and PKC pathways, which both can be triggered by EGF, although at different time points, have opposite effects on SPRR2A gene expression [8].
• SPR2B protein quantities were moderately increased while SPR2A was not significantly changed [11].

Analytical, diagnostic and therapeutic context of SPRR2A

• Deletion mapping and site-directed mutagenesis of SPRR2A promoter-chloramphenicol acetyltransferase constructs indicate that four transcription control elements are essential and sufficient for promoter activity [3].
• Expression of SPRR2A and ENDOA/CK8, two epithelium-specific ESE-1 target genes, were revealed by RT-PCR in all cases [1].

References