RT Journal Article
SR Electronic
T1 Rab40c regulates focal adhesions and PP6 activity by controlling ANKRD28 ubiquitylation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101346
DO 10.26508/lsa.202101346
VO 5
IS 9
A1 Ke-Jun Han
A1 Valeryia Mikalayeva
A1 Scott A Gerber
A1 Arminja N Kettenbach
A1 Vytenis A Skeberdis
A1 Rytis Prekeris
YR 2022
UL https://www.life-science-alliance.org/content/5/9/e202101346.abstract
AB Rab40c is a SOCS box–containing protein which binds Cullin5 to form a ubiquitin E3 ligase complex (Rab40c/CRL5) to regulate protein ubiquitylation. However, the exact functions of Rab40c remain to be determined, and what proteins are the targets of Rab40c-Cullin5–mediated ubiquitylation in mammalian cells are unknown. Here we showed that in migrating MDA-MB-231 cells Rab40c regulates focal adhesion’s number, size, and distribution. Mechanistically, we found that Rab40c binds the protein phosphatase 6 (PP6) complex and ubiquitylates one of its subunits, ankyrin repeat domain 28 (ANKRD28), thus leading to its lysosomal degradation. Furthermore, we identified that phosphorylation of FAK and MOB1 is decreased in Rab40c knock-out cells, which may contribute to focal adhesion site regulation by Rab40c. Thus, we propose a model where Rab40c/CRL5 regulates ANKRD28 ubiquitylation and degradation, leading to a decrease in PP6 activity, which ultimately affects FAK and Hippo pathway signaling to alter focal adhesion dynamics.