ATP6AP1 (ATPase H+ Transporting Accessory Protein 1)

This study highlights probable hub genes, drugs targeting them, and associated pathways perturbed by SARS-CoV-2 NSP6. Galectin3 (LGALS3) upregulated in both heart and brain after COVID-19 infection is reported to be influencing all the ten hallmarks of cancer. Our bioinformatics and systems study hints probable effect of COVID-19 infection in cancer incidence and warrants in-depth studies for present scenario of long and recurrent COVID-19.

The mechanism may be that SSR4 regulates the expression of NDUFB11 and ATP6AP1, and then enhanced the function of mitochondrial respiratory chain complex I (CI) and mitochondrial respiratory chain complex V (CV), which promoted the mitochondrial oxidative phosphorylation and thus promoted GC progression. These findings expand the understanding of the role of SSR4 and provide a new target for the treatment of GC.

Histologically, they present a characteristic morphology, which may require differential diagnosis from other granular cell entities, including benign conditions (such as histiocyte-rich inflammatory reactions) and malignant neoplasms such as the histiocytoid variant of lobular carcinoma or apocrine carcinoma. We present a case of granular cell tumour of the breast, radiologically classified as BI-RADS 5, to highlight the importance of morphological and immunohistochemical studies for establishing a definitive diagnosis.

In our study, the machine learning-trained diagnostic model (AUC = 0.998) and the identified pyroptosis-related core gene ATP6AP1 provided an actionable strategy to overcome immune resistance in HCC. Mechanistically, ATP6AP1 stabilizes V-ATPase, which acidifies lysosomes, impairs antigen presentation, and drives pyroptotic inflammasome activation. This study highlights that ATP6AP1 plays a key role in promoting the lysosomal acidisis-pyroptosis-immunosuppression axis, and targeting ATP6AP1 can reshape the TME and enhance the efficacy of immunotherapy in HCC patients.

Remarkably, ATP6AP1 induces lysosomal acidification through the regulation of V-ATPase assembly and facilitates autophagosome-lysosome fusion by enhancing the interaction between Rab7 and the HOPS complex. Together, our studies identify ATP6AP1 as a crucial regulator of autophagy, potentially serving as a valuable prognostic marker or therapeutic target in human luminal breast cancer.

NDUFAB1, VDAC1, TYMP, UGDH, ATP6AP1, and ALDH2 showed consistent and significant expression differences between the BC and control groups. This study's identification of key prognostic genes and the development of a risk model offer potential new targets for therapeutic intervention and clinical management of BC.

Doxorubicin-induced cytotoxicity is associated with autophagy flux in breast cancer. The lysosomal gene ATP6AP1 facilitates autolysosome acidification and contributes to doxorubicin resistance in breast cancer.

Our study demonstrates the power of DAE analysis and daeQTL mapping to identify causal regulatory variants and target genes at breast cancer risk loci, including those with complex regulatory landscapes. It additionally provides a genome-wide resource of variants associated with DAE for future functional studies.

With the aim of studying V-ATPase-related mutations using the yeast model system, we report that Big1 is another homolog of ATP6AP1 in yeast cells, and we characterize the role of Big1 in maintaining a fully functional V-ATPase. In addition to its role in acidifying the vacuole or lysosome, our data support the concept that the V-ATPase may function as part of a signaling pathway to regulate macroautophagy/autophagy through a mechanism that is independent from Tor/MTOR.

Our results indicated that amplifications of these genes may play an important etiological role in teratoma formation. Moreover, amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1, found on array comparative genomic hybridization, may help to explain the characteristics of teratomas in chondrogenesis and osteogenesis.

Heterozygous mutation of TNFSF11 was also associated with a slightly increased expression of genes involved in osteoclast proliferation and differentiation, including Tcirg1, Junb, Anxa2, and Atp6ap1. Overall, we demonstrate that single gene mutations in Tnfsf11 cause bone resorption instability without significantly altering the genes related to osteoblast and osteoclast activity in the bone marrow cavity, thus establishing an optimal resource as an experimental animal model for bone resorption in bone biology research.

Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors...In fact, targeting the ATP6AP1 C-tail could block Rheb activation and inhibit cancer cell proliferation and migration. Our findings highlight the versatility of PhastID in mapping transient PPIs in live cells, reveal ATP6AP1's role as an unconventional GEF for Rheb, and underscore the importance of ATP6AP1 in integrating mTORC1 activation signals through Rheb, filling in the missing link in Rheb/mTORC1 activation.