The WASH complex is a regulator of the actin nucleator Arp2/3 and is involved in the trafficking of receptors from the endosome. FAM21, its largest subunit, has a key role in WASH function and also mediates WASH complex assembly. In addition, the long tail of FAM21 has been shown to interact with a number of factors that are involved in receptor trafficking. Zhi-Hui Deng, Daniel Billadeau and co-workers (p. 373) now make use of a FAM21 deletion mutant that does not associate with known interaction partners to identify new binding partners. Surprisingly, they find components of the nuclear factor κB (NF-κB) pathway, including the NF-κB subunits p65 and p50. Furthermore, their data suggest that FAM21 forms new complexes with p65 and p50 independent of the WASH complex and, indeed, depletion of FAM21, but not WASH, decreased the expression of NF-κB target genes. Interestingly, FAM21 depletion sensitises pancreatic cancer cells to chemotherapeutic drugs. The authors also address the molecular mechanism of this new FAM21 function and show that it does not affect the nuclear translocation of NF-κB. Instead, FAM21 interacts with p65 in the nucleus, where it might affect transcriptional activity of the NF-κB pathway at least in part at the level of p65 recruitment to chromatin. Taken together, the data presented here point to a new and unanticipated function of FAM21 in the nucleus – a role it fulfils outside of the WASH complex – that opens new avenues of research, in particular with regard to the possible contribution of FAM21 to cancer cell survival.
A nuclear function for FAM21 outside of WASH
A nuclear function for FAM21 outside of WASH. J Cell Sci 15 January 2015; 128 (2): e0202. doi:
Download citation file:
Advertisement
Cited by
Call for papers - Cilia and Flagella: from Basic Biology to Disease
We are welcoming submissions for our upcoming special issue: Cilia and Flagella: from Basic Biology to Disease. This issue will be coordinated by two Guest Editors: Pleasantine Mill (University of Edinburgh) and Lotte Pedersen (University of Copenhagen). Submission deadline: 1 March 2025.
Biologists @ 100 - join us in Liverpool in March 2025
We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register your interest to join us in March 2025 in Liverpool, UK.
Principles and regulation of mechanosensing
Mechanics play a fundamental role in cell physiology and represent physical mechanisms which cells use to influence function from the molecular to tissue scale. In this Review, Stefano Sala and colleagues clearly define mechanosensing and mechanotransduction, illustrate various mechanosensing mechanisms and discuss methods that cells use to regulate these processes.
JCS-FocalPlane Training Grants
Early-career researchers - working in an area covered by JCS - who would like to attend a microscopy training course, please apply. Deadline dates for 2024 applications: 7 September (decision by week commencing 8 October 2024); 22 November (decision by week commencing 16 December).
HIV-1 assembly – when virology meets biophysics
Claire Lacouture and colleagues review mechanisms of assembly of the HIV-1 structural protein Gag from biophysical and biological perspectives. The researchers highlight how HIV-1 Gag hijacks host cell factors associated with cortical actin machinery to make new viral particles.