A primate-specific POTE-actin fusion protein plays a role in apoptosis

Abstract

The primate-specific gene family, POTE, is expressed in many cancers but only in a limited number of normal tissues (testis, ovary, prostate). The 13 POTE paralogs are dispersed among 8 human chromosomes. They evolved by gene duplication and remodeling from an ancestral gene, Ankrd26, recently implicated in controlling body size and obesity. In addition, several POTE paralogs are fused to an actin retrogene producing POTE-actin fusion proteins. The biological function of the POTE genes is unknown, but their high expression in primary spermatocytes, some of which are undergoing apoptosis, suggests a role in inducing programmed cell death. We have chosen Hela cells as a model to study POTE function in human cancer, and have identified POTE-2alpha-actin as the major transcript and the protein it encodes in Hela cells. Transfection experiments show that both POTE-2alpha-actin and POTE-2gammaC are localized to actin filaments close to the inner plasma membrane. Transient expression of POTE-2alpha-actin or POTE-2gammaC induces apoptosis in Hela cells. Using wild-type and mutant mouse embryo cells, we find apoptosis induced by over-expression of POTE-2gammaC is decreased in Bak ( -/- ) or Bak ( -/- ) Bax ( -/- ) cells indicating POTE is acting through a mitochondrial pathway. Endogenous POTE-actin protein levels but not RNA levels increased in a time dependent manner by stimulation of death receptors with their cognate ligands. Our data indicates that the POTE gene family encodes a new family of proapoptotic proteins.

A genome-wide analysis of gene–caffeine consumption interaction on basal cell carcinoma

“…POTE is a highly homologous gene family located on numerous chromosomes and expressed in a wide variety of human cancers (colon, lung, breast, ovary and pancreas) (48). In normal tissue, its expression is restricted to testis, ovary and prostate, with the highest expression in testis (49). Little is known about the biological function of this gene family, but there is evidence for its role in inducing programmed cell death (49).…”

“…In normal tissue, its expression is restricted to testis, ovary and prostate, with the highest expression in testis (49). Little is known about the biological function of this gene family, but there is evidence for its role in inducing programmed cell death (49).…”

Proteomics-based identification of secreted protein dihydrodiol dehydrogenase 2 as a potential biomarker for predicting cisplatin efficacy in advanced NSCLC patients

“…Some of these proteins have previously been reported to be related with chemoresistance of cancers; results that support the findings of our study. Most of them are functional proteins, such as Fumarate hydratase [15,16], Phosphodiesterase [17,18], POTE-2␣-actin [19][20][21], S100A10 [22,23], Prefoldin 2 [24,25] and Karyopherin [26,27], which may lead to drug resistance through stress response, metabolism, cell signaling, cell proliferation and apoptosis. Among these proteins, overexpression and cellular distribution of DDH2 were confirmed by real-time PCR, Western blot and immunohistochemistry.…”

“…There was no significant difference of DDH2 expression between CR + PR and SD subgroups (3.529 vs. 3.982 ng/mL). The serum levels of DDH2 showed an upward tendency after cisplatin-based chemotherapy (at the time of enrollment, after two and after four cycles of treatment) in the different therapy outcome subgroups such as CR + PR (3.529 vs. 9.635 vs. 19.882 ng/mL, P < 0.001), SD (3.982 vs. 11.998 vs. 16.923 ng/mL, P < 0.001) and PD (9.036 vs. 17.171 ng/mL, P < 0.001), respectively. There were no significant differences of DDH2 expression according to age, gender, stage, histology, smoking history, or chemotherapy regimen.…”

Ankrd26 Gene Disruption Enhances Adipogenesis of Mouse Embryonic Fibroblasts

“…ANKRD26 is the ancestral gene for a primate-specific gene family POTE (3). POTE appears to be a proapoptotic gene that is highly expressed in testis and only in a few other normal tissues but is expressed in many cancers (4,5). The ANKRD26 gene is much larger than POTE and contains many more exons.…”