Disease relevance of SFN

• RACK1 and stratifin target DeltaNp63alpha for a proteasome degradation in head and neck squamous cell carcinoma cells upon DNA damage [1].
• Compared with normal mammary epithelial cells, expression of HME1 RNA was dramatically low in two cell lines derived from human mammary carcinoma that were examined, and in a line of normal mammary epithelial cells transformed by oncogenes [2].
• A newborn female child developed SFN after dystocic delivery causing cerebral frontal lobe hemorrhage [3].
• Subcutaneous fat necrosis of the newborn (SFN) is an uncommon disease that affects newborns who have suffered from tissue hypoxia during or following delivery [3].
• Claudin-4, mitogen-activated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions [4].

High impact information on SFN

• We further demonstrate that mice that are compound heterozygotes for mutations in Irf6 and the gene encoding the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show similar defects of keratinizing epithelia [5].
• In this report, we demonstrate that the interaction of epithelial cell marker E-cadherin with integrin alpha(E)(CD103)beta(7), often expressed by tumor-infiltrating lymphocytes (TILs), plays a major role in effective tumor cell lysis [6].
• Hypermethylation of 14-3-3 sigma (stratifin) is an early event in breast cancer [7].
• Furthermore, proteomic profiling of HLCECs and human conjunctival epithelial cells (HCECs) identified a 14-3-3 protein (stratifin) preferentially expressed by HLCECs [8].
• In keratinocytes, 14-3-3sigma (stratifin) is involved in terminal differentiation and its cell cycle function in this cell type might diverge from the one it fulfills in other cellular backgrounds [9].

Chemical compound and disease context of SFN

• Accumulation of folic acid-albumin FITC occurs in ascites tumour cells expressing the epithelial cell marker EMA, with a significant proportion of EMA negative cells also accumulating the conjugate [10].

Biological context of SFN

• Subsequently, western blot analysis revealed phosphorylation of p38 at 90 min after stratifin stimulation and this was decreased to approximately 50% of the maximum value by 120 min [11].
• Our data indicated that treatment of dermal fibroblasts with stratifin resulted in rapid and transient upregulation of c-jun and c-fos mRNA levels [11].
• The complete identity of the sequenced peptides from stratifin with the amino acid sequence translated from the stratifin cDNA clone indicated that this cDNA codes for stratifin [12].
• Moreover, siRNA knockdown of both stratifin and RACK1 inhibited a nuclear export and protein degradation of DeltaNp63alpha, respectively [1].
• However, the tissue distribution, arrangement of charged amino acids, and location of potential phosphorylation sites of HME1 differ from those of 14-3-3 [2].

Anatomical context of SFN

• Previously, we have demonstrated that keratinocyte releasable stratifin, also known as 14-3-3 sigma protein, stimulates matrix metalloproteinase (MMP)-1 expression in dermal fibroblasts [11].
• Stratifin, however, was present only in cultured epithelial cells and was most abundant in fetal and adult human tissues enriched in stratified squamous keratinising epithelium [12].
• A polyclonal antibody to the epithelial cell marker cytokeratin was used to identify trophoblast cells [13].
• E-FABP and 14-3-3-sigma (stratifin) was found to be overexpressed only in the mitoxantrone-selected atypical multidrug-resistant cell line [14].
• Lymphoid and epithelial cell marker studies based on paired immunofluorescence staining were performed on ethanol-fixed specimens from six Warthin's tumors of the parotid gland [15].

Associations of SFN with chemical compounds

• We also demonstrated that SB203580 (SB), a specific inhibitor of p38 MAPK activity, inhibited the activation of fibroblast MMP-1 mRNA expression by stratifin [11].
• However, stratifin binds with phosphorylated DeltaNp63alpha in response to cisplatin [1].
• The HME1 sequence has extensive sequence homology with bovine 14-3-3 protein, which is an activator of tyrosine and tryptophan hydroxylase [2].
• Annotated transcripts known to be involved in development and also potentially regulated by estrogen (cytokeratins 8 and 18, stratifin, midkine, and glycolytic enzymes) were further analyzed by real-time PCR [16].

Regulatory relationships of SFN

• In conclusion, stratifin stimulates fibroblast MMP-1 levels through the activation of c-fos and MAPK pathway [11].
• The results of a dose-response experiment showed that stratifin stimulates the expression of stromelysin-1 (MMP-3) mRNA by dermal fibroblasts in a concentration-dependent fashion [17].

Other interactions of SFN

• Furthermore, SB significantly blocked the stratifin induction of MMP-1 protein levels (***p<0.005, n=3) [11].
• Our results indicate that stratifin markedly increase Elk4/Sap1 mRNA expression in a time-dependent fashion [11].
• Upon DNA damage induced by cisplatin, stratifin mediated a nuclear export of DeltaNp63alpha into cytoplasm and then RACK1 targeted latter into a proteasome degradation pathway possibly serving as an E3 ubiquitin ligase [1].
• Immunofluorescence staining of keratinocytes showed that two of these proteins (IEF SSPs 9124 and 9126) localize to the Golgi apparatus, while stratifin is distributed diffusely in the cytoplasm [12].
• Our initial attempt using the candidate gene approach did not yield any somatic mutations in the 14-3-3sigma gene (official gene symbol, SFN), a mediator of G2 arrest by TP53 [18].

Analytical, diagnostic and therapeutic context of SFN

• Microarray analysis of stratifin-treated fibroblasts shows an increase in Elk4/Sap1 mRNA expression and this finding was confirmed by northern blot analysis [11].
• Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway [12].
• A sequential chromatography of the active fractions of keratinocyte-conditioned medium (KCM) and peptide mapping of the candidate proteins identified KDAF as being the keratinocyte-releasable 14-3-3 sigma (14-3-3sigma) protein, which is also known as stratifin [19].
• The present report demonstrates its usefulness as an epithelial cell marker in DNA flow cytometry of archival specimens [20].
• Microarray analysis of ERRP-treated HCT-116 cells showed reduced levels of several growth regulatory proteins such as p21Rac1, Stratifin (14-3-3 Sigma), focal adhesion kinase (FAK) and mediators of the Ras-Raf-ERK pathway [21].

References