2 research outputs found
Role-Shifting PKCζ Fosters Its Own Proapoptotic Destruction by Complexing with Bcl10 at the Nuclear Envelope of Human Cervical Carcinoma Cells: A Proteomic and Biochemical Study
Many features of deadly human cervical cancers (HCCs)
still require
elucidation. Among HCC-derived cell lines, here we used the C4-I one
since its quantitative gene expression pattern most closely mimics
invasive HCCs, including protein kinase-Cζ (PKCζ) overexpression.
Via proteomic, bioinformatic, and biochemical approaches we identified
31 and 33 proteins co-immunoprecipitating with PKCζ from nuclear
membranes (NMs) of, respectively, untreated or VP-16-exposed C4-I
cells. Such proteins belonged to eight functional groups, whose compositions
and relative sizes changed with either context. Of the 56 proteins
identified, only eight were shared between the two subproteomes, including
Bcl10. Surprisingly, proteins known to associate with Bcl10, like
Carma1/3 and Malt1, in so-called CBM signalosomes were absent. Notably,
in VP-16-treated C4-I cells, PKCζ•Bcl10 complexes increasingly
accrued at NMs, where PKCζ phosphorylated Bcl10, as PKCζ
also did <i>in vitro</i> and in cell-free systems, both
processes being thwarted by interfering RNA (<i>i</i>RNA)
PKCζ depletion. Caspase-3 was associated with PKCζ•Bcl10
complexes and proteolyzed PKCζ leading to its inactivation/destruction;
both events were prevented by Bcl10 iRNA suppression. Thus, PKCζ’s
molecular interactions and functional roles changed strikingly according
to the untreated or apoptogen-treated cells context, and by complexing
with Bcl10, PKCζ surprisingly favored its own demise, which
suggests both proteins as HCCs therapeutic targets