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Truncated trafficking protein TRAPPC6A(del29‐42) counteracts tumor suppressor WOX1‐mediated apoptosis
Author(s) -
Chang JeanYun,
Chang NanShan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.526.4
Subject(s) - microbiology and biotechnology , cytoplasm , immunoprecipitation , golgi apparatus , suppressor , chemistry , apoptosis , ectopic expression , transport protein , biology , endoplasmic reticulum , biochemistry , gene
Whether apoptosis occurs during abnormal protein trafficking is largely unknown. Here, we isolated a TGF‐beta1‐induced truncated trafficking protein particle complex 6A, TRAPPC6A(del29‐42), which bound tumor suppressor WOX1 (also named WWOX or FOR). The wild type TRAPPC6A is a component of transport protein particle (TRAPP) complex in vesicle trafficking to the Golgi complex. Transient overexpression of TRAPPC6A(del29‐42) induced apoptosis of oral SCC‐15 and many other types of cells. Ectopic TRAPPC6A(del29‐42) is localized in the cytoplasm and nucleus. By co‐immunoprecipitation, endogenous WOX1 interacted with TRAPPC6A. Also, by FRET analysis, TRAPPC6A(del29‐42) physically bound to the C‐terminal SDR domain of WOX1. TRAPPC6A(del29‐42) counteracts with WOX1 in inducing apoptosis probably due to direct binding. We determined the presence of WOX1/TRAPPC6A aggregates in the hippocampus of patients with Alzheimer's disease (AD). Importantly, TGF‐beta1 induced aggregation of WOX1 and TRAPPC6A in vitro, indicating a novel mechanism for the pathogenesis of AD. [Supported by NSC 96‐2628‐B‐006‐045‐MY3, 96‐2628‐B‐006‐041‐MY3, NHRI EX97‐9705BI, Taiwan, and DoD BC075692, USA].