The ABC of glycosylation

Perego, Paola; Gatti, Laura; Beretta, Giovanni Luca

doi:10.1038/nrc2789-c1

Cited by 29 publications

(16 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased levels of glycosylation-defective transporters of the ABC superfamily have been reported in ovarian carcinoma cells with acquired resistance to cisplatin and oxaliplatin, and characterized by impaired drug accumulation . It is still a matter of debate how such transporters act to increase Pt drug efflux, and one cannot exclude the possibility that they play an indirect role in drug efflux (Fletcher et al, 2010;Perego et al, 2010).…”

Section: Distribution Of Platinum Compounds In Sub-cellular Compartmementioning

confidence: 99%

New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants

Gatti

Cassinelli

Zaffaroni

et al. 2015

Drug Resistance Updates

Self Cite

View full text Add to dashboard Cite

Section: Distribution Of Platinum Compounds In Sub-cellular Compartmementioning

confidence: 99%

New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants

Gatti

Cassinelli

Zaffaroni

et al. 2015

Drug Resistance Updates

Self Cite

View full text Add to dashboard Cite

“…In addition, P-gp is subjected to post-translational modifications, in particular glycosylation in the Golgi apparatus, to form the mature core glycosylated protein. Previous studies suggested that glycosylation protects P-gp from degradation and mislocalization (Fu and Arias, 2012; Perego et al, 2010). Strategic localization of P-gp at the luminal membrane of BBB endothelial cells and its wide substrate selectivity make it an effective defense against a wide spectrum of endogenous ligands, therapeutic drugs and xenobiotics (Miller et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Mrp4 seems to be expressed on both the luminal and abluminal membranes of the rat brain capillary endothelium. Similar to P-gp, MRPs are made of two homologous and highly conserved six-transmembrane proteins interconnected by a central cytoplasmic linker domain and they are subjected to glycosylation that protects MRPs from degradation and mislocalization (Chang, 2007; Perego et al, 2010). They also contain an additional membrane-spanning domain.…”

Section: Introductionmentioning

confidence: 99%

Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

et al. 2015

View full text Add to dashboard Cite

The strength of the blood-brain barrier (BBB) in providing protection to the central nervous system from exposure to circulating chemicals is maintained by tight junctions between endothelial cells and by a broad range of transporter proteins that regulate exchange between CNS and blood. The most important transporters that restrict the permeability of large number of toxins as well as therapeutic agents are the ABC transporters. Among them, P-gp, BCRP, MRP1 and MRP2 are the utmost studied. These efflux transporters are neuroprotective, limiting the brain entry of neurotoxins; however, they could also restrict the entry of many therapeutics and contribute to CNS pharmacoresistance. Characterization of several regulatory pathways that govern expression and activity of ABC efflux transporters in the endothelium of brain capillaries have led to an emerging consensus that these processes are complex and contain several cellular and molecular elements. Alterations in ABC efflux transporters expression and/or activity occur in several neurological diseases. Here, we review the signaling pathways that regulate expression and transport activity of P-gp, BCRP, MRP1 and MRP2 as well as how their expression/activity changes in neurological diseases.

show abstract

“…Indeed, functional studies indicated that resistance was unrelated to ER function, but directly induced by IGFR-1R signalling through activation of different survival kinases including ERK [53]. Moreover, although the role of glycomic alterations in cancer and their relevance in cell survival are poorly understood [54], a recent report indicates that fucosyltransferase IV (FUT4) overexpression, which is associated with increased levels of the anti-apoptotic protein Bcl-2 and decreased levels of pro-apoptotic proteins, up-regulates ERK1/2 and Akt. The anti-apoptotic effect of FUT4 observed in cells treated with the alkylating agent cyclophosphamide could be blocked by specific pathway inhibitors, including the MEK inhibitor PD98059 [55].…”

Section: Erk1/2mentioning

confidence: 97%

Modulation of Sensitivity to Antitumor Agents by Targeting the MAPK Survival Pathway

Cossa¹,

Gatti²,

Cassinelli³

et al. 2013

Current Pharmaceutical Design

Self Cite

View full text Add to dashboard Cite

Mitogen-activated protein kinases (MAPK) are involved in a complex network which regulates a variety of cellular processes including proliferation, survival and death. The molecular characterization of the pathway has shown aberrant activation in several human tumors, due to the deregulation of receptor tyrosine kinases or to mutations of pathway components. Progress in understanding the MAPK network has led to the development of target-specific agents in clinical trials. The relevance of MAPK in response and resistance to antitumor agents has been recognized, although the outcome of MAPK activation can vary depending on the molecular background of tumor cells and on the type of activated kinase. The canonical cascade of MAPK, i.e., depending on the Extracellular Signal-Regulated Kinases (ERK), can act in protective signalling pathways, thereby limiting DNA damage. Since tumor cell survival can be sustained by ERK and cross talk of ERK with other pathways, modulation of sensitivity to antitumor agents by targeting the ERK cascade appears to be an amenable approach. Indeed, ERK play a role in resistance to both cytotoxic and target-specific agents. Preclinical studies support the relevance of drug combination approaches to enhance the efficacy of antitumor treatments. Combinations of pharmacological inhibitors of the ERK cascade and conventional or target-specific antitumor agents may be helpful in an attempt to overcome drug resistance. A deeper understanding of the genetic alterations of tumor cells and of tumor heterogeneity as well as of drug resistance mechanisms is expected to contribute to the rational design of MAPK-mediated drug combinations that will lead to reversal of drug resistance.

show abstract

The ABC of glycosylation

Cited by 29 publications

References 11 publications

New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants

New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants

Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

Modulation of Sensitivity to Antitumor Agents by Targeting the MAPK Survival Pathway

Contact Info

Product

Resources

About