DC-STAMP interacts with ER-resident transcription factor LUMAN which becomes activated during DC maturation.
Dendritic cells (DCs) are the professional antigen-presenting cells (APC) which efficiently prime the immune response or induce tolerance. We recently identified Dendritic Cell Specific TrAnsMembrane Protein (DC-STAMP), a novel 470 amino acid protein preferentially expressed by dendritic cells. Previously we demonstrated that DC-STAMP re-localizes towards the Golgi upon DC maturation. To identify proteins that interact with DC-STAMP, a yeast-2-hybrid analysis was performed. Here, we report a physically interacting partner of DC-STAMP in the endoplasmic reticulum (ER), called LUMAN (also known as CREB3 or LZIP). LUMAN was previously described as an ER-resident transcription factor with unknown function. It is activated in a process called regulated intramembrane proteolysis (RIP), which involves translocation to the Golgi and subsequent proteolytic cleavage. The proteolytically activated form of the protein then translocates to the nucleus. Our data indicate that DC-STAMP plays an important role in the modulation of LUMAN activation. Moreover, we demonstrate that LUMAN is endogenously expressed by DC and becomes activated by RIP upon DC maturation induced by various different stimuli. These data define LUMAN/DC-STAMP as a novel regulatory circuit in DC.
Eleveld-Trancikova
Dagmar
D
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Sanecka
Anna
A
van Hout-Kuijer
Maaike A
MA
Looman
Maaike W G
MW
Hendriks
Ilona A M
IA
Jansen
Bastiaan J H
BJ
Adema
Gosse J
GJ
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D012333:RNA, Messenger / Q000032:analysis
D048868:Adaptor Proteins, Signal Transducing; C107941:CREB3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C501589:DCSTAMP protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger