The Human Bcl-2 Family Member Bcl-rambo Localizes to Mitochondria and Induces Apoptosis and Morphological Aberrations in Drosophila

Abstract

Bcl-2 family proteins play a central role in regulating apoptosis. We previously reported that human Bcl-rambo, also termed BCL2L13, localized to mitochondria and induced apoptosis when overexpressed in human embryonic kidney 293T cells. However, the physiological function of Bcl-rambo currently remains unclear. In the present study, human Bcl-rambo was ectopically expressed in Drosophila melanogaster. Bcl-rambo mainly localized to the mitochondria of Drosophila Schneider 2 (S2) cells. The overexpression of Bcl-rambo, but not Bcl-rambo lacking a C-terminal transmembrane domain, induced apoptosis in S2 cells. Moreover, the ectopic expression of Bcl-rambo by a GAL4-UAS system induced aberrant morphological changes characterized by atrophied wing, split thorax, and rough eye phenotypes. Bcl-rambo induced the activation of effector caspases in eye imaginal discs. The rough eye phenotype induced by Bcl-rambo was partly rescued by the co-expression of p35, Diap1, and Diap2. By using this Drosophila model, we showed that human Bcl-rambo interacted genetically with Drosophila homologues of adenine nucleotide translocators and the autophagy-related 8 protein. The results of the present study demonstrated that human Bcl-rambo localized to mitochondria and at least regulated an apoptosis signaling pathway in Drosophila.

Role of Bcl-rambo in Apoptosis and Mitophagy

“…After ectopically expressing Bcl-rambo in Drosophila, induction of caspase activity was detected in the eye imaging disc of the third instar larvae. The chrysalis showed abnormal phenotype with chest fissure, wing atrophy and rough eye, while there was no significant change in the pupillary retina at the same time [22], suggesting that Bcl-rambo has a stronger pro-apoptotic role in the active cells than in the quiescent cells [26]. Analysis of embryos obtained from in vitro fertilization (IVF) indicates that Bcl-rambo is constitutively expressed during early human embryonic development; however, the cellular localization alteration during its physiological activities is a curious phenomenon [27,28].…”

“…It is surprising that it preserves the pro-apoptotic activity, which might due to its Alu element [21]. On the other hand, Bcl-rambo is highly expressed in a variety of tumors, including childhood acute lymphoblastic leukemia (ALL), gastric cancer, liposarcoma and glioblastoma [22]. However, incompatible to its pro-apoptotic function, elevated expression of Bcl-rambo is strongly associated with poor prognosis in cancer [23].…”

Anti‑Condyloma acuminata mechanism of microRNAs‑375 modulates HPV in cervical cancer cells via the UBE3A and IGF‑1R pathway

“…Modern molecular biology technology has identified >100 HPV subtypes, 34 of which are associated with CA; the most common subtypes include HPV6, HPV11, HPV16 and HPV18 (12). Based on differences in pathogenicity, HPV subtypes are divided into low-risk and high-risk genotype groups, with low-risk genotypes (HPV6 and 11) primarily causing genital warts, including Condyloma, and high-risk genotypes (HPV16 and 18) being associated with genital neoplasms (2). In the present study, miRNA-375 overexpression suppressed cell proliferation and increased LDH activity in HPV-18(+) cervical cancer cells, compared with the negative group.…”

“…CA grows rapidly and recurs easily and it causes physical pain and psychological issues in patients. HPV is a type of epithelial DNA virus, which has many subtypes, among which HPV6 and HPV11 cause CA (2,3). CA is caused by the epithelial-associated proteins found in the genomes of each subtype (2,3).…”

Lactobacillus raises in vitro anticancer effect of geniposide in HSC‑3 human oral squamous cell carcinoma cells

“…The Bcl-2 family is made up of the apoptosis inhibitory factors Bcl-2 and Bcl-xL, and the apoptosis-promoting factor Bax, and their ratio determines whether the cell is able to accept the apoptotic signal (17). To a certain extent, apoptosis or apoptosis inhibition are regulated by the above two genes.…”