RESUMEN
p300 is an important transcriptional co-factor. By stimulating the transfer of acetyl residues onto histones and several key transcription factors, p300 enhances transcriptional initiation and impacts cellular processes including cell proliferation and cell division. Despite its importance for cellular homeostasis, its regulation is poorly understood. We show that TRIM25, a member of the TRIM protein family, targets p300 for proteasomal degradation. However, despite TRIM25's RING domain and E3 activity, degradation of p300 by TRIM25 is independent of TRIM25-mediated p300 ubiquitination. Instead, TRIM25 promotes the interaction of p300 with dynein, which ensures a microtubule-dependent transport of p300 to cellular proteasomes. Through mediating p300 degradation, TRIM25 affects p300-dependent gene expression.
RESUMEN
The tripartite motif (TRIM) protein family is attracting increasing interest in oncology. As a protein family based on structure rather than function, a plethora of biological activities are described for TRIM proteins, which are implicated in multiple diseases including cancer. With hormone-driven cancers being among the leading causes of cancer-related death, TRIM proteins have been described to portrait tumor suppressive or oncogenic activities in these tumor types. This review describes the biological impact of TRIM proteins in relation to hormone receptor biology, as well as hormone-independent mechanisms that contribute to tumor cell biology in prostate, breast, ovarian and endometrial cancer. Furthermore, we point out common functions of TRIM proteins throughout the group of hormone-driven cancers. An improved understanding of the biological impact of TRIM proteins in cancer may pave the way for improved prognostication and novel therapeutics, ultimately improving cancer care for patients with hormone-driven cancers.
