Endocytic proteins in the regulation of nuclear signaling, transcription and tumorigenesis

Abstract

A B S T R A C TAccumulating evidence argues that many proteins governing membrane sorting during endocytosis participate also in nuclear signaling and transcriptional regulation, mostly by

Epigenetic inactivation of the tumor suppressor BIN1 drives proliferation of SNF5-deficient tumors

“…44,52,53 Finally, while the cellular function of BIN1 is not completely understood, its ability to interact with many binding partners through its SH3 domain and its ability to translocate to the nucleus suggests that BIN1 may be an example of a bridge between epigenetic gene regulation and transduction of multiple types of extracellular signals. 30,54,55 Disruption of such coordinated signaling activity following SNF5 loss would be analogous to our finding that upstream control of Hedgehog signaling becomes uncoupled from Hedgehog target gene transcription in the absence of SNF5, using comparative marker selection (two-sided t-test with 1,000 permutations).…”

Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization

“…Porcine TP, structurally similar to TPa but containing an additional C-terminal serine residue [51], does internalize following agonist challenge. Post-ligand receptors bound to arrestin in clathrin-coated pits are internalized within early endosomes, and rapidly recycled back to the membrane surface; or in late (perinuclear) endosomes, destined for degradation or for nuclear transit [52,53]. Membrane fractions resolved from postnuclear supernatants by high-speed centrifugation contain early and late endosomes, and cytosolic fractions may contain late endosomes [54,55].…”

A Snapshot of the Physical and Functional Wiring of the Eps15 Homology Domain Network in the Nematode

“…While these interactions need further validation and confirmation of their relevance, they are in line with the reported presence of EH-containing and EH-binding proteins, such as Eps15 or epsin [47], [49], in the nucleus of mammalian cells. The nuclear localization of these latter proteins is itself suggestive of a wider connection between endocytosis (or endocytic proteins) and nuclear functions, whose biological significance remains largely to be ascertained [50], [53], [86], [87].…”

“…Third, EH-network proteins are also involved in the organization of the actin cytoskeleton [7], [8], [45]. Finally, a number of EH-containing and EH-interacting proteins shuttle in and out of the nucleus [32], [47]–[49], where they might participate in the control of transcription or of other nuclear events [7], [8], [45], [50]. In summary, the EH network appears to integrate several physiological functions and its subversion is involved in relevant pathological conditions, including cancer [51]–[53].…”