Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis.

Aberrant regulation of ubiquitination often leads to metabolic reprogramming in tumor cells. However, the underlying mechanisms are not fully understood. Here we demonstrate that OTUB2, an OTU deubiquitinase, is upregulated in colorectal cancer (CRC) and exacerbates the progression of CRC through modulating the aerobic glycolysis.

Structure and functions of cellular redox sensor HSCARG/NMRAL1, a linkage among redox status, innate immunity, DNA damage response, and cancer.

NmrA-like proteins are NAD(P) (H) interacting molecules whose structures are similar to that of short-chain dehydrogenases. In this review, we focus on an NADP(H) sensor, HSCARG (also named NMRAL1), which is a NmrA-like protein that is widely present in mammals, and provide a comprehensive overview of the current knowledge of its structure and physiological functions. HSCARG selectively binds to the reduced form of type II coenzyme NADPH via its Rossmann fold domain.

Cellular redox sensor HSCARG negatively regulates the translesion synthesis pathway and exacerbates mammary tumorigenesis.

The translesion synthesis (TLS) pathway is a double-edged sword in terms of genome integrity. Deficiency in TLS leads to generation of DNA double strand break (DSB) during replication stress, while excessive activation of the TLS pathway increases the risk of point mutation. Here we demonstrate that HSCARG, a cellular redox sensor, directly interacts with the key protein PCNA in the TLS pathway.

Ribosomal protein L6 (RPL6) is recruited to DNA damage sites in a poly(ADP-ribose) polymerase-dependent manner and regulates the DNA damage response.

Ribosomal proteins are the building blocks of ribosome biogenesis. Beyond their known participation in ribosome assembly, the ribosome-independent functions of ribosomal proteins are largely unknown. Here, using immunoprecipitation, subcellular fractionation, His-ubiquitin pulldown, and immunofluorescence microscopy assays, along with siRNA-based knockdown approaches, we demonstrate that ribosomal protein L6 (RPL6) directly interacts with histone H2A and is involved in the DNA damage response (DDR).

A20/TNFAIP3 Regulates the DNA Damage Response and Mediates Tumor Cell Resistance to DNA-Damaging Therapy.

A competent DNA damage response (DDR) helps prevent cancer, but once cancer has arisen, DDR can blunt the efficacy of chemotherapy and radiotherapy that cause lethal DNA breakage in cancer cells. Thus, blocking DDR may improve the efficacy of these modalities. Here, we report a new DDR mechanism that interfaces with inflammatory signaling and might be blocked to improve anticancer outcomes.