A Novel Intracellular Peptide Derived from G1/S Cyclin D2 Induces Cell Death

Abstract

Background: Intracellular peptides probably regulate several biological processes. Results: pep5 derived from G 1 /S cyclin D2 specifically increases during the S phase of the cell cycle and, reintroduced into the cell, induces apoptosis and necrosis. Conclusion: pep5 has potential therapeutic applications and could have biological functions. Significance: pep5 discovery advances our understanding of limited proteolysis.

Peptidomic analysis of the anterior temporal lobe and corpus callosum from schizophrenia patients

“…Noteworthy is that Pep5 derived from G1/S cyclin D2 of the HeLa cell cycle was capable of inducing cell death in vitro and also in vivo when tested in rat C6 glioblastoma [14]. Furthermore, in another recent report peptide AGH, a fragment of the hemoglobin alphachain, inhibited peripheral inflammatory hyperalgesic responses through indirect activation of mμ opioid receptors (MOR), indicating a potential to control inflammatory chronic pain [61].…”

“…Examples of peptide actions include binding to proteins and activating or inhibiting their activity [11]. Peptidomic approaches have been used to examine the effects of proteasome inhibitors on the peptide content of HEK293T and SH-SY5Y cells [12] as well as in neurolysin-knockout mice [13] and in the identification of a new intracellular peptide, pep5-cpp, which reduced by 50% the volume of rat C6 glioblastoma [14].…”

A Cyclin D2-derived peptide acts on specific cell cycle phases by activating ERK1/2 to cause the death of breast cancer cells

“…Previous peptidomic studies performed in HeLa cells demonstrated a variation in the intracellular peptide profile at different phases of the cell cycle [15]. Among the identified peptides, a peptide named pep5, which originated from Cyclin D2, is increased in S phase of the cell cycle [15].…”

“…Among the identified peptides, a peptide named pep5, which originated from Cyclin D2, is increased in S phase of the cell cycle [15]. Cyclin D2 is degraded by the UPS during the G1/S transition of the cell cycle [16], suggesting that pep5 can be generated endogenously at this transition state of the cell cycle.…”

“…Cyclin D2 is degraded by the UPS during the G1/S transition of the cell cycle [16], suggesting that pep5 can be generated endogenously at this transition state of the cell cycle. A synthetic pep5 fused to a cell penetrating peptide (cpp), or pep5-cpp, induced cell death in different cell lines in vitro and reduced the rat C6 glioblastoma volume by almost 50% in vivo [15].…”