The hippo kinase STK38 ensures functionality of XPO1

Abstract

The proper segregation of basic elements such as the compartmentalization of the genome and the shuttling of macromolecules between the nucleus and the cytoplasm is a crucial mechanism for homeostasis maintenance in eukaryotic cells. XPO1 (Exportin 1) is the major nuclear export receptor and is required for the export of proteins and RNAs out of the nucleus. STK38 (also known as NDR1) is a Hippo pathway serine/threonine kinase with multifarious functions in normal and cancer cells. In this review, we summarize the history of the discovery of the nucleo/ cytoplasmic shuttling of proteins and focus on the major actor of nuclear export: XPO1. After describing the molecular events required for XPO1-mediated nuclear export of proteins, we introduce the Hippo pathway STK38 kinase, synthetize its regulation mechanisms as well as its biological functions in both normal and cancer cells, and finally its intersection with XPO1 biology. We discuss the recently identified mechanism of XPO1 activation by phosphorylation of XPO1_S1055 by STK38 and contextualize this finding according to the biological functions previously reported for both XPO1 and STK38, including the second identity of STK38 as an autophagy regulator. Finally, we phrase this newly identified activation mechanism into the general nuclear export machinery and examine the possible outcomes of nuclear export inhibition in cancer treatment.

Caprin-1 influences autophagy-induced tumor growth and immune modulation in pancreatic cancer

“…STK38 supports the interaction of Exo84 with Beclin1 and RalB which is required for the initiation of autophagosome [ 42 , 43 ]. Depletion of STK38 displays the impaired LC3B conversion and reduces ATG14L, ATG12, and WIPI-1 puncta formation [ 44 ]. Our findings demonstrate that Carpin-1 interacts with ULK1 and inhibits the phosphorylation of ULK1 that accelerates the initiation of autophagosome.…”