Background: Breast cancer autoantigen nucleolar GTP-binding protein-1 (NGP-1) is overexpressed in cancers. Results: NGP-1 promotes G 1 to S phase transition by modulating the p53/p21 pathway. Conclusion: CDK inhibitor, p21, enhances cell proliferation in certain situations. Significance: This study provides evidence that p21 induces cell proliferation in addition to its traditional tumor suppressor function.

is a proto-oncogene controlling expression of multiple genes involved in cell growth and differentiation. Although the functional role of c-Myc as a transcriptional regulator has been intensively studied, targeting this protein in cancer remains a challenge. Here, we report a trimodal regulation of c-Myc function by the Ras effector, Ras-association domain family member 7 (RASSF7), a nonenzymatic protein modulating protein-protein interactions to regulate cell proliferation. Using HEK293T and HeLa cell lines, we provide evidence that RASSF7 destabilizes the c-Myc protein by promoting Cullin4B-mediated polyubiquitination and degradation. Furthermore, RASSF7 competed with MYC-associated factor X (MAX) in the formation of a heterodimeric complex with c-Myc and attenuated its occupancy on target gene promoters to regulate transcription. Consequently, RASSF7 inhibited c-Myc-mediated oncogenic transformation, and an inverse correlation between the expression levels of the and genes was evident in human cancers. Furthermore, we found that RASSF7 interacts with c-Myc via its RA and leucine zipper (LZ) domains and LZ domain peptide is sufficient to inhibit c-Myc function, suggesting that this peptide might be used to target oncogenic c-Myc. These results unveil that RASSF7 and c-Myc are functionally linked in the control of tumorigenesis and open up potential therapeutic avenues for targeting the "undruggable" c-Myc protein in a subset of human cancers.

RAS proteins are major human oncogenes, and most of the studies are focused on enzymatic RAS effectors. Recently, nonenzymatic RAS effectors (RASSF, RAS association domain family) have garnered special attention because of their tumor-suppressive properties in contrast to the oncogenic potential of the classical enzymatic RAS effectors. Whereas most members of RASSF family are deregulated by promoter hypermethylation, RASSF8 promoter remains unmethylated in many cancers but the mechanism(s) of its down-regulation remains unknown. Here, we unveil E4BP4 as a critical transcriptional modulator repressing RASSF8 expression through histone methyltransferases, G9a and SUV39H1. In line with these observations, we noticed a negative correlation of RASSF8 and E4BP4 expression in primary breast tumor samples. In addition, our data provide evidence that E4BP4 attenuates RASSF8-mediated anti-proliferation and apoptosis, shedding mechanistic insights into RASSF8 down-regulation in breast cancers. Collectively, our study provides a better understanding on the epigenetic regulation of RASSF8 function and implicates the development of better treatment strategies.

Development of effective therapeutic strategies to combat COVID-19 relies on understanding the cellular and molecular mechanisms of infection. Antibodies specific to SARS-CoV-2 aid in accelerating research to characterize viral protein function and immune response to infection. An urgent need for SARS-CoV-2 specific antibodies arose, as several antibodies already available in the market cross-reacted with other members of the coronavirus family. To address this need for specificity and urgency, we collaborated with a leading pharmaceutical company to develop antibodies specific to SARS-CoV-2. We generated a single chain fragment variable (scFv) library for SARS-CoV-2 using computational expansion of published antibody structures against SARS-CoV-1. This enabled us to make recombinant antibodies in record time of 3 months. These synthetic sequences were grafted onto both human and human-rabbit chimeric Fc enabling use of these antibodies in a multitude of immunoassays. Our antibodies were targeted against the SARS-CoV-2 spike protein; the receptor binding domain in the spike protein plays a vital role in viral entry into host cells and subsequent infection, making it an important target for neutralizing antibodies and antiviral treatments. Some of our antibodies demonstrate neutralizing capabilities, making them a valuable tool to study neutralizing antibody response to infection. These antibodies are specific to SARS-CoV-2 and do not cross-react with other coronaviruses. The specificity and versatility of our antibodies enables scientists to better understand SARS-CoV-2 and potentially aid in developing therapeutic strategies against COVID-19 which continues to be important as newer variants of the virus emerge.