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2017 ; 6
(10
): e387
Nephropedia Template TP
Tang J
; Zhan MN
; Yin QQ
; Zhou CX
; Wang CL
; Wo LL
; He M
; Chen GQ
; Zhao Q
Oncogenesis
2017[Oct]; 6
(10
): e387
PMID28991259
show ga
Aberrant activation of nuclear factor-?B (NF-?B) has been observed in a wide
range of human cancers and is thought to promote tumorigenesis and metastasis. As
a central component of NF-?B pathway, p65 protein level is tightly regulated and
could be subjected to proteasome degradation. Here we demonstrated that p65 can
bind to HSC70 with four consensus recognition motif in its RHD domain and be
constitutively transported to the lysosome membrane to bind with
lysosome-associated membrane protein type 2A and degraded within the lysosome in
two epithelial cell lines, proposing that p65 can be degraded by
chaperone-mediated autophagy (CMA). Of great importance, there is a decreased CMA
activity together with impaired degradation of p65 in a process of
epithelial-mesenchymal transition (EMT). The resulted accumulation of p65 leads
to higher NF-?B activity and contributes to the progression and maintenance of
the EMT program. Taken together, our results define a novel regulatory mechanism
for the important transcription factor p65, and these findings would shed new
light on the inhibition of EMT, as well as metastasis of cancer cells.