Proteolytic processing of human serum albumin generates EPI‐X4, an endogenous antagonist of CXCR4

[摘要] ThechemokinereceptorCXCR4isanimportantGprotein‐coupledreceptor.SignalingviaCXCL12regulatesanumberofimportantbiologicprocesses,includingimmuneresponses,organogenesis,orhematopoiesis.DysregulationofCXCR4signalingisassociatedwithavarietyofdiseases,suchascancerdevelopmentandmetastasis,immunodeficiencies,orchronicinflammation.Here,wereviewourfindingsonendogenouspeptideinhibitorofCXCR4asanovelantagonistofCXCR4.Thispeptideisa16‐residuefragmentofhumanserumalbuminandwasisolatedasaninhibitorofCXCR4‐tropichumanimmunodeficiencyvirustype1fromablood‐derivedpeptidelibrary.EndogenouspeptideinhibitorofCXCR4bindsthesecondextracellularloopofCXCR4,therebypreventingengagementofCXCL12andantagonizingthereceptor.Consequently,endogenouspeptideinhibitorofCXCR4inhibitsCXCL12‐mediatedmigrationofCXCR4‐expressingcellsinvitro,mobilizeshematopoieticstemcells,andsuppressesinflammatoryresponsesinvivo.WediscussthegenerationofendogenouspeptideinhibitorofCXCR4,itsrelevanceasbiomarkerfordisease,anditsroleinhumanimmunodeficiencyvirus/acquiredimmunodeficiencysyndromepathogenesisandcancer.Furthermore,wediscusswhyoptimizedendogenouspeptideinhibitorofCXCR4derivativesmighthaveadvantagesoverotherCXCR4antagonists...

[学科分类] 生理学

[关键词] HIV‐1;inflammation;signaling;cellular migration;metastasis