TGFb type I receptor and endosomal APPL regulate AURKB during mitosis and cytokinesis

• The cytokine transforming growth factor b(TGFb) suppressescell proliferationand promotesapoptosis1. It signalsvia specific serine/threonine kinase receptors, i.e.TGFbtype I (TbRI) and type II (TbRII) receptors2,3,causing growth arrest of normal epithelial cells. However, TGFbis often overexpressed inadvanced cancers,and promotes proliferation of tumour cells and their invasion. The intracellular domain (ICD) of TbRI is cleaved offin cancer cells,and is translocated to the nucleus in an APPL1/2-dependent manner, drivingan invasiveness program4.The specific mechanism(s) whereby cancer cells escape pro-apoptotic signals induced by TGFbremainspoorly understood. Here, we report that TbRI and APPL1/2 proteins orchestrate this escape via the pro-survival protein survivin and Aurora kinase B (AURKB), a key regulatorof mitosis and chromosomal stability5. We show that TbRI and APPL1/2 control expression of AURKB and that TbRI-ICDand AURKB form a complex during the telophase in PC-3Uprostate cancerand KELLY neuroblastomacells. APPL1/2 and TbRI also form a complex with survivin, a pro-survival protein. The identified TbRI–AURKB-survivinpathwayrepresents a novel function for TbRI to promote survival and cell division of cancer cells.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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