The JNK/AP-1 pathway upregulates expression of the recycling endosome rab11a gene in B cells transformed by Theileria.
Lymphocyte transformation induced by Theileria parasites involves constitutive activation of c-Jun N-terminal kinase (JNK) and the AP-1 transcription factor. We found that JNK/AP-1 activation is associated with elevated levels of Rab11 protein in Theileria-transformed B cells. We show that AP-1 regulates rab11a promoter activity in B cells and that the induction of c-Jun activity in mouse fibroblasts also leads to increased transcription of the endogenous rab11a gene, consistent with it being an AP-1 target. Pharmacological inhibition of the JNK pathway reduced Rab11 protein levels and endosome recycling of transferrin receptor (TfR) and siRNA knockdown of JNK1 and Rab11A levels also reduced TfR surface expression. We propose a model, where activation of the JNK/AP-1 pathway during cell transformation might assure that the regulation of recycling endosomes is co-ordinated with cell-cycle progression. This might be achieved via the simultaneous upregulation of the cell cycle machinery (e.g. cyclin D1) and the recycling endosome regulators (e.g. Rab11A).
Lizundia
Regina
R
Laboratory of Comparative Cell Biology of Apicomplexan Parasites, Département de Maladie Infectieuse, Institut Cochin, Inserm, U567, CNRS, UMR 8104, Faculté de Médecine René Descartes, Université Paris Descartes, UMR-S 8104, Paris, 75014 France.
Chaussepied
Marie
M
Naissant
Bernina
B
Masse
Guillemette X
GX
Quevillon
Emmanuel
E
Michel
Fréderique
F
Monier
Solange
S
Weitzman
Jonathan B
JB
Langsley
Gordon
G
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000469:parasitology; D002417:Cattle; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism*; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D008213:Lymphocyte Activation; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D016796:Theileria annulata / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000502:physiology*; D015854:Up-Regulation; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D000099193:rab11 GTP-Binding Proteins
D048031:JNK Mitogen-Activated Protein Kinases; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins