Palmitoyltransferase ZDHHC3 is essential for the oncogenic activity of PML/RARα in acute promyelocytic leukemia.

The oncogenic fusion protein promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα) is critical for acute promyelocytic leukemia (APL). PML/RARα initiates APL by blocking the differentiation and increasing the self-renewal of leukemic cells. The standard clinical therapies all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which induce PML/RARα proteolysis, have dramatically improved the prognosis of APL patients.

The palmitoyltransferase ZDHHC21 regulates oxidative phosphorylation to induce differentiation block and stemness in AML.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of patients who receive the most intensive treatment inevitably experience disease relapse, likely resulting from the persistence of drug-resistant leukemia stem cells (LSCs). AML cells, especially LSCs, are highly dependent on mitochondrial oxidative phosphorylation (OXPHOS) for survival, but the mechanism involved in OXPHOS hyperactivity is unclear, and a noncytotoxic strategy to inhibit OXPHOS is lacking.

Short message service usage may improve the public's self-health management: A community-based randomized controlled study.

Background And Aims: The last decade has witnessed unprecedented growth in mobile phone use. It links millions of previously unconnected people. The ubiquity of mobile phones, which allows for use of the short message service (SMS), offers new and innovative opportunities for disease prevention and health education.

Blockade of deubiquitinase YOD1 degrades oncogenic PML/RAR and eradicates acute promyelocytic leukemia cells.

In most acute promyelocytic leukemia (APL) cells, promyelocytic leukemia (PML) fuses to retinoic acid receptor (RAR) due to chromosomal translocation, thus generating PML/RAR oncoprotein, which is a relatively stable oncoprotein for degradation in APL. Elucidating the mechanism regulating the stability of PML/RAR may help to degrade PML/RAR and eradicate APL cells. Here, we describe a deubiquitinase (DUB)-involved regulatory mechanism for the maintenance of PML/RAR stability and develop a novel pharmacological approach to degrading PML/RAR by inhibiting DUB.

Deneddylation of PML/RARα reconstructs functional PML nuclear bodies via orchestrating phase separation to eradicate APL.

Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML/RARα, which destroys the architecture of PML nuclear bodies (NBs). PML NBs are critical to tumor suppression, and their disruption mediated by PML/RARα accelerates APL pathogenesis. However, the mechanisms of PML NB disruption remain elusive.

Protein phase separation: A novel therapy for cancer?

In recent years, phase separation has been increasingly reported to play a pivotal role in a wide range of biological processes. Due to the close relationships between cancer and disorders in intracellular physiological function, the identification of new mechanisms involved in intracellular regulation has been regarded as a new direction for cancer therapy. Introducing the concept of phase separation into complex descriptions of disease mechanisms may provide many different insights.