Salivary protein histatin 3 regulates cell proliferation by enhancing p27(Kip1) and heat shock cognate protein 70 ubiquitination

Biochemical and Biophysical Research Communications
Yasuhiro ImamuraNorio Sogawa

Abstract

Histatins are salivary proteins with antimicrobial activities. We previously reported that histatin 3 binds to heat shock cognate protein 70 (HSC70), which is constitutively expressed, and induces DNA synthesis stimulation and promotes human gingival fibroblast (HGF) survival. However, the underlying mechanisms of histatin 3 remain largely unknown. Here, we found that the KRHH sequence of histatin 3 at the amino acid positions 5-8 was essential for enhancing p27(Kip1) (a cyclin-dependent kinase inhibitor) binding to HSC70 that occurred in a dose-dependent manner; histatin 3 enhanced the binding between p27(Kip1) and HSC70 during the G1/S transition of HGFs as opposed to histatin 3-M(5-8) (substitution of KRHH for EEDD in histatin 3). Histatin 3, but not histatin 3-M(5-8), stimulated DNA synthesis and promoted HGF survival. Histatin 3 dose-dependently enhanced both p27(Kip1) and HSC70 ubiquitination, whereas histatin 3-M(5-8) did not. These findings provide further evidence that histatin 3 may be involved in the regulation of cell proliferation, particularly during G1/S transition, via the ubiquitin-proteasome system of p27(Kip1) and HSC70.

References

Jan 1, 1990·Journal of Dental Research·R F TroxlerF G Oppenheim
Jan 1, 1988·Annual Review of Genetics·S Lindquist, E A Craig
Dec 1, 1985·Molecular and Cellular Biology·K O'MalleyL Kedes
Aug 25, 1995·The Journal of Biological Chemistry·I M TakenakaL E Hightower
May 1, 1995·Molecular and Cellular Biology·M OhtsuboM Pagano
Jan 14, 1994·Biochemical and Biophysical Research Communications·Y MurakamiA Tsunemitsu
Feb 18, 1994·Science·D SchmidP Christen
Apr 4, 1997·The Journal of Biological Chemistry·B BercovichA Ciechanover
Jun 1, 1997·Genes & Development·R J SheaffB E Clurman
Jul 22, 1998·Cell Stress & Chaperones·E ZeiseL Rensing
Dec 22, 1998·Acta Odontologica Scandinavica·J Tenovuo
Apr 13, 1999·Biochemical and Biophysical Research Communications·S NakamuraA Hirai
Sep 24, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A S Lundberg, R A Weinberg
Mar 11, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A S Lundberg, R A Weinberg
May 23, 2003·The Journal of Biological Chemistry·Xuewei S LiMira Edgerton
Jan 28, 2004·Cell·Andrew W Murray
Apr 17, 2004·The Journal of Biological Chemistry·Yasuhiro ImamuraDaisuke Kitamura
Mar 3, 2005·Genes & Development·Mikkel RohdeMarja Jäättelä
Apr 12, 2007·Cell Cycle·Adriana BorrielloFulvio Della Ragione

❮ Previous
Next ❯

Citations

Jun 3, 2021·International Journal of Molecular Sciences·Sachio Tsuchida, Tomohiro Nakayama

❮ Previous
Next ❯

Related Concepts

Related Feeds

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.