PAK4 Kinase Activity Plays a Crucial Role in the Podosome Ring of Myeloid Cells

Foxall, Elizabeth; Staszowska, Adela; Hirvonen, L; Georgouli, Mirella; Ciccioli, Mariacristina; Rimmer, Alexander; Williams, Lynn; Calle, Yolanda; Sanz-Moreno, Victoria; Cox, Susan M.; Jones, Gareth E.; Wells, Claire M.

doi:10.1016/j.celrep.2020.107593

Cited by 2 publications

(1 citation statement)

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“…PAKs, as important downstream effectors of CDC42, are involved in regulating the phosphorylation level of JNK and p38 [53][54][55]. In the kinase domain, phosphorylation of the unique threonine residue (Thr423 in human PAK1 and Thr474 in human PAK4) is essential for full catalytic activity [56,57]. Therefore, we speculated that the effect of CDC42 K153R acetylation on the phosphorylation of JNK and p38 might be mediated by PAK.…”

Section: Plos Pathogensmentioning

confidence: 99%

Bacterial infection promotes tumorigenesis of colorectal cancer via regulating CDC42 acetylation

Wang

et al. 2023

PLoS Pathog

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Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.

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