An expanded role for dipeptidyl peptidase 4 in cell regulation

Abstract

Purpose of review Dipeptidyl peptidase 4 (DPP4) is a serine protease with diverse regulatory functions in healthy and diseased cells. Much remains unknown about the mechanisms and targets of DPP4. Here we discuss new studies exploring DPP4-mediated cellular regulation, provide an updated list of potential targets of DPP4, and discuss clinical implications of each. Recent findings Recent studies have sought enhanced efficacy of targeting DPP4's role in regulating hematopoietic stem and progenitor cells for improved clinical application. Further studies have identified DPP4 functions in different cellular compartments and have proposed ways to target this protein in malignancy. These findings, together with an expanded list of putative extracellular, cell surface, and intracellular DPP4 targets, provide insight into new DPP4-mediated cell regulation. Summary DPP4 posttranslationally modifies proteins and peptides with essential roles in hematopoietic cell regulation, stem cell transplantation, and malignancy. Targets include secreted signaling factors and may include membrane proteins and transcription factors critical for different hematopoietic functions. Knowing these targets and functions can provide insight into new regulatory roles for DPP4 that may be targeted to enhance transplantation, treat disease, and better understand different regulatory pathways of hematopoiesis.

Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein

“…This implies that a separate host cell receptor may be interacting with SARS-CoV-2 S protein, underscoring the need to screen for additional host receptors that may facilitate infection. Indeed, it has been postulated that this and other coronaviruses such as SARS-CoV and MERS-CoV can infect host cells via S protein binding to cell surface receptors that are not their "primary" receptor [42][43][44][45][46]. Second, in this study, PB cells and HSCs/HPCs are only being exposed to SARS-CoV-2 protein, not the full viral particle, which indicates that SARS-CoV-2 may impact cells regardless of whether viral entry actually occurs in these cells.…”

Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?

“…More in depth information on DPP4 during the aging process is clearly warranted. There are many proteins that have purported DPP4-truncation sites [ 358 , 359 ]. This is of relevance as DPP4-trucated proteins can have decreased activity and block the effects of the full length molecules [ 352 , 360 ].…”

Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT‑4/lactate‑mediated intracellular acidosis

“…Dipeptidyl-peptidase-4 (DPP-4) is a ubiquitously expressed transmembrane exopeptidase found on the surface of numerous hematopoietic cells ( 12 ). DPP-4 has sparked scientific interest over the last 10 years, with numerous studies describing its role in tumor immunology and the prognosis of patients with cancer ( 13-16 ). Various DPP-4 inhibitors are used to treat type II diabetes with an absence of serious side effects ( 17 ).…”