K63-Linked Ubiquitination in Kinase Activation and Cancer

Ubiquitination has been demonstrated to play a pivotal role in multiple biological functions, which include cell growth, proliferation, apoptosis, DNA damage response, innate immune response, and neuronal degeneration. Although the role of ubiquitination in targeting proteins for proteasome-dependent degradation have been extensively studied and well-characterized, the critical non-proteolytic functions of ubiquitination, such as protein trafficking and kinase activation, involved in cell survival and cancer development, just start to emerge, In this review, we will summarize recent progresses in elucidating the non-proteolytic function of ubiquitination signaling in protein kinase activation and its implications in human cancers. The advancement in the understanding of the novel functions of ubiquitination in signal transduction pathways downstream of growth factor receptors may provide novel paradigms for the treatment of human cancers

Emerging cellular functions of cytoplasmic PML

The tumor suppressor promyelocytic leukaemia protein (PML) is located primarily in the nucleus, where it is the scaffold component of the PML nuclear bodies (PML-NBs). PML-NBs regulate multiple cellular functions, such as apoptosis, senescence, DNA damage response and resistance to viral infection. Despite its nuclear localization, a small portion of PML has been identified in the cytoplasm. The cytoplasmic PML (cPML) could be originally derived from the retention of exported nuclear PML (nPML). In addition, bona fide cPML isoforms devoid of nuclear localization signal (NLS) have also been identified. Recently, emerging evidence showed that cPML performs its specific cellular functions in tumorigenesis, glycolysis, antiviral responses, laminopothies and cell cycle regulation. In this review, we will summarize the emerging roles of cPML in cellular functions