Regulation of p63 Protein Stability via Ubiquitin-Proteasome Pathway

Table 1

Regulators of p63 protein stability. +: positively regulates p63 protein stability; −: negatively regulates p63 protein stability. *: MDM2 functions as not an E3 ligase here, but a helper to promote translocation of ΔNp63α to cytoplasm [35].

Regulators	Stability regulation	p63 isoform	Interaction or modification sites	References
E3 ligases
Nedd4	−	ΔNp63α	PPPY motif in SAM domain	[36]
Itch	−	ΔNp63𝛼	PPPY motif in SAM domain	[26]
	−	All p63 isoforms	A region encompassing aminoacids 109 to 120 of TAp63 (aminoacids 15 to 26 of ΔNp63)	[37]
WWP1	−	p63α	PPPY motif in SAM domain	[42]
Fbw7	−	ΔNp63α	Likely a region encompassing S383 of ΔNp63α	[35]
Pirh2	−	TAp63 and ΔNp63		[47, 48]
Kinase
ATM	−	ΔNp63α	S385 of ΔNp63α	[49]
CDK2	−	ΔNp63α	T397 of ΔNp63α	[49]
p70s6K	−	ΔNp63α	S466 of ΔNp63α	[49]
IKK𝛽	+	TAp63𝛾	TAD of TAp63𝛾	[51]
	−	ΔNp63α	Unknown	[52]]
HIPK2	−	ΔNp63α	T397 of TAp63𝛾	[55]
c-Abl	+	TAp63	Y149, Y171, and Y289 of TAp63	[22]
	−	ΔNp63α	Y55, Y137, and Y308 of ΔNp63α	[58]
Plk1	−	TAp63	S52 of TAp63	[59]
p38	−	ΔNp63α	Unknown	[60]
GSK3	−	ΔNp63α	S383 of ΔNp63α	[35]
Raf1	−	ΔNp63α	S383 or T397 of ΔNp63α	[16]
Others
Gadd45a	−	ΔNp63α	No direct interaction	[60]
p53	−	ΔNp63α	DBD of ΔNp63α	[29]
MDM2*	−	ΔNp63α	SAM domain	[35]
Cabbles1	+	TAp63α	TAD and SAM of TAp63α	[65]
YAP	+	ΔNp63α	PPPY motif in SAM domain	[58]
Dlx3	−	ΔNp63α	No direct interaction	[16]
Stratifin	−	p63α	RQTISFP motif in TID of p63α	[61]
RACK1	−	p63α	C-ter of p63α	[61]
Stxbp4	+	ΔNp63α	PPPY motif in SAM domain	[64]
Ubc9	−	ΔNp63α	K582 of ΔNp63α	[36]
PML	+	p63α	Unknown	[66]
Pin1	+	p63α	PPPY motif in SAM domain	[67]