Cooperation of salivary protein histatin 3 with heat shock cognate protein 70 relative to the G1/S transition in human gingival fibroblasts.

Abstract

Histatins, a family of salivary proteins, have antimicrobial activity. Candida albicans, which is killed by histatins, induces oral candidiasis in individuals with compromised immune systems. Although the functional significance of histatins has been documented, their biological and physiological functions against host cells have not been clarified. In this study, we found that histatin 3, a member of the histatin family, binds to heat shock cognate protein 70 (HSC70). These proteins were co-localized in the cytoplasm and nucleus in human gingival fibroblasts following non-heat and heat shock. Histatin 3 induced stimulation of DNA synthesis and cell survival in human gingival fibroblasts in a dose-dependent manner. This DNA synthesis was found to be dependent on HSC70 by knockdown experiments. The effect of heat shock on DNA synthesis induced by histatin 3 was approximately 2-fold higher than that of non-heat shock. When the histatin 3 uptake into cells was inhibited by monodansylcadaverine or when histatin 3 binding to HSC70 was precluded by 15-deoxyspergualin, DNA synthesis by histatin 3 was approximately 2-fold less than that without monodansylcadaverine or 15-deoxyspergualin. Although HSC70 directly bound to p27(Kip1) (a cyclin-dependent kinase inhibitor), histatin 3 increased the binding between those proteins but not with a peptide capable of binding to HSC70. Moreover histatin 3 prevented ATP-dependent dissociation of HSC70-p27(Kip1). ATP was unable to form a histatin 3-HSC70(D10N)-p27(Kip1) complex (HSC70(D10N) is a mutant attenuating ATPase activity). These findings suggest that histatin 3 may be involved in cell proliferation through the regulation of HSC70 and p27(Kip1) in oral cells.

• Authors: Yasuhiro Imamura, Yoshihisa Fujigaki, Yuriko Oomori, Syuhei Usui, Pao-Li Wang
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 21 Pg. 14316-25 (May 22 2009) ISSN: 0021-9258 [Print] United States
• PMID: 19321452 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Guanidines
• HSC70 Heat-Shock Proteins
• HTN3 protein, human
• Histatins
• Salivary Proteins and Peptides
• Cyclin-Dependent Kinase Inhibitor p27
• Adenosine Triphosphate
• DNA
• gusperimus

Topics

• Adenosine Triphosphate (pharmacology)
• Cell Survival (drug effects)
• Cyclin-Dependent Kinase Inhibitor p27 (metabolism)
• DNA (biosynthesis)
• Fibroblasts (cytology, drug effects, metabolism)
• G1 Phase (drug effects)
• Gene Knockdown Techniques
• Gingiva (cytology)
• Guanidines (pharmacology)
• HSC70 Heat-Shock Proteins (chemistry, metabolism)
• Heat-Shock Response (drug effects)
• Histatins (metabolism)
• Humans
• Protein Binding (drug effects)
• Protein Structure, Tertiary
• Protein Transport (drug effects)
• S Phase (drug effects)
• Salivary Proteins and Peptides (metabolism)