Regulation of apoptosis by a Caenorhabditis elegans BNIP3 homolog

Abstract

We have identi®ed a C. elegans protein, ceBNIP3, homologous to the human BCL-2/EIB-19K interacting BCL-2 family pro-apoptotic protein BNIP3. In transiently transfected mammalian cells, ceBNIP3 complexes with CED-9, the worm homolog of BCL-2. CeBNIP3 also eciently heterodimerizes with the cell death protease proCED-3 by direct binding via the prodomain. Transfection of ceBNIP3 and CED-3 results in enhanced proteolytic processing of the CED-3 zymogen and in cooperative induction of apoptosis. Coexpression of CED-9 suppresses the cooperative cell death induced by ceBNIP3 and CED-3. In cells coexpressing CED-9, ceBNIP3 and CED-3, all three proteins exist as a ternary complex suggesting that CED-9 may suppress cooperative apoptosis induced by CED-3 and ceBNIP3 by simultaneous complex formation with CED-3 and ceBNIP3. Our results suggest that ceBNIP3 may be a novel component of the C. elegans apoptosis paradigm and may initiate apoptosis by recruiting CED-3 to mitochondria and other cytoplasmic membranes.

C. elegans ced-13 can promote apoptosis and is induced in response to DNA damage

“…We identified three such peptides: one corresponded to the EGL-1 protein, a second corresponded to the C. elegans Bnip3 protein, 33 and a third was encoded by a genomic fragment of cosmid R09F10 not previously annotated as an open reading frame (ORF) (Figure 1a). To determine whether the region of R09F10 identified was part of a protein-coding gene, we inspected the genomic sequence manually and assembled a putative gene structure.…”

Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans

“…In addition, due to their size, some ZnONPs may reach the nucleus and interact with DNA molecules (Sharma et al, 2012a,b;Martinez et al, 2003). Several genes are biomarkers of the DNA damage and apoptosis, such as p53 (Derry et al, 2001) and BNIP3 (Yasuda et al, 1998;Pinkston-Gosse Kenyon, 2007), the orthologs of C. elegans cep-1 and dct-1, respectively. The observed increase in transcript levels of cep-1 (in wild-type and the triple mutant) and dct-1 (in wild-type only) following a ZnONP challenge suggests that exposure and apoptosis are interlinked, and supports the notion that zinc oxide nanoparticles can induce apoptosis in human cancer cells through reactive oxygen species 57…”

Functional identification of the apoptosis effector BH3 domain in cellular protein BNIP1

“…Among the latter three proteins, BNIP3 has been shown to be a member of the`BH3-alone' proteins (Yasuda et al, 1998a). BNIP3 (Yasuda et al, 1998a;Chen et al, 1997) and its human homolog BNIP3a (Yasuda et al, 1999, Chen et al, 1999Matsushima et al, 1998) as well as the C. elegans homolog, ceBNIP3 (Yasuda et al, 1998b), promote apoptosis. BNIP2 appears to be related to the signaling molecule RhoGAP (Boyd et al, 1994) and it has opposing e ects on apoptosis, depending on the stimuli (X Gong and G Chinnadurai, in preparation).…”