Death-associated protein 3 (DAP3) is a highly conserved guanosine triphosphate (GTP) binding protein. As a component of the mitochondrial ribosome 28 S small subunit, DAP3 is involved in apoptosis pathways and plays a vital role in mitochondrial dynamics, mitochondrial protein synthesis, anoikis, and autophagy. Recently, DAP3 has been reported to participate in the development and progression of various cancers. In this review, we provide a brief overview of recent findings regarding the structure, subcellular localization, and function of DAP3 as well as its role in cancer development and progression.
The significance of telomere/telomerase biology in the pathogenesis of age-related cardiovascular diseases (CVDs), such as atherosclerosis, hypertension, myocardial infarction (MI), and heart failure, has been increasingly highlighted in recent years. The activation of the DNA damage response (DDR) due to the presence of short telomeres is believed to be a significant upstream signal responsible for inducing a permanent cessation of the cell cycle in cardiomyocytes. Heart failure (HF) is a condition that arises due to the restricted regenerative capacity of the elderly and injured mammalian heart. This limitation may be related to the decreased proliferative potential of cardiac stem cells (CSCs) and cardiomyocytes. The association between CVDs and shorter telomeres provides a foundation for developing therapeutic techniques aimed at elongating telomeres and subsequently restoring the proliferative ability of the adult mammalian heart. This phenomenon offers intriguing prospects for the treatment and prevention of cardiovascular disease (CVD). Further investigation into telomerase gene therapy in the field of cardiac regenerative medicine is justified based on the encouraging outcomes shown in mice models, whereby the reactivation of telomerase in the heart after MI has demonstrated beneficial effects.
Ara-A, Ara-C, Ara-G, and Ara-T are arabinose sugars combined with adenine, cytosine, guanine, and thymine bases, respectively. These drugs are clinically important as these drugs are commonly used as anti-viral and anti-cancer drugs. Ara-C, an arabinoside, serves as a chain terminator of deoxyribonucleic acid (DNA) replication by interfering with replication after it is incorporated at the 3′ end of nascent DNA, thereby restricting the proliferation of viruses and cancer cells. The incorporated Ara-CMP is efficiently removed by the proofreading exonuclease activity of polymerase epsilon (Polε), in which the alternative clamp loader CTF18 plays a pivotal role. However, the requirement of CTF18 for the removal of the other arabinosides from the 3′ end of nascent DNA remains unclear. Here, we explored DNA repair pathways responsible for the cellular tolerance to Ara-A and found that cells deficient in the proofreading exonuclease activity of Polε (POLE1 exo−/−) showed the highest sensitivity to Ara-A. This activity was also required for cellular tolerance to Ara-G and Ara-T. CTF18 −/− cells showed higher Ara-A sensitivity than wild-type cells, though it was critically lower than that of POLE1 exo−/− cells. Similar trends were observed for the sensitivity to Ara-G and Ara-T. These results indicate that these arabinosides are removed by Polε proofreading exonuclease activity, and CTF18 is pivotal for Polε-mediated Ara-C removal but does not play critical roles for Polε-mediated removal of Ara-A, Ara-G, and Ara-T. In this study, we unveiled a difference between Ara-C and the other arabinosides (Ara-A, Ara-G, and Ara-T) in the removal from the 3′ end of nascent DNA.
The inhibition of KIF18A selectively reduces the viability of chromosomally unstable cancers due to increased mitotic vulnerability. KIF18A expression was also reported to be upregulated and associated with tumor aggressiveness in certain cancer types including breast cancer. Here, I first showed that KIF18A mRNA expression is higher in triple-negative breast cancer (TNBC) than in non-TNBC. I also found that ER (estrogen receptor)-negative and PR (progesterone receptor)-negative breast cancer cells have higher KIF18A mRNA expression compared to ER-positive and PR-positive breast cancer cells, respectively. In contrast, HER2-positive breast tumors have higher KIF18A expression compared to HER2-negative breast tumors. In terms of PAM50 breast cancer subtypes, KIF18A transcript levels were found to be the highest in basal-like breast cancer, followed by HER2-enriched, luminal B, normal-like and luminal A. Besides, in non-TNBC, cells with high AR (androgen receptor) mRNA expression have higher KIF18A mRNA expression than cells with low AR mRNA expression. Both non-TNBC and TNBC cells with high BRCA1 and BRCA2 mRNA expression levels were observed to have higher KIF18A mRNA expression than those with low BRCA1 and BRCA2 mRNA expression levels, respectively. Combined, this study demonstrates that breast tumors with low and high expression of ER, PR, HER2, AR and BRCA1/2 have differential transcript levels of KIF18A, pointing that KIF18A might contribute to the molecular differences between different breast cancer subtypes.