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Table 1 Post-translational modification controlling hippo pathway core components

From: New insights into posttranslational modifications of Hippo pathway in carcinogenesis and therapeutics

Core component (D. melanogaster protein) Enzyme Regulatory sites Function
MST1/2 (Hpo) PI3K/Akt1 T120-p, T387-p Prevention of caspase-mediated cleavage of MST1
Autophosphorylation T183-pa MST activation
JNK1 S82-p Enhancement of MST1-mediated pro-apoptotic signaling
mTOR T120-p Loss of MST1 function
c-Abl Y433-p Inhibition of degradation
TAO3b   MST activation
PP2A T183-depa  
CHIP Ubiquitination Protein degradation
SAV1 (Sav) MST2  T26-p, S27-p, S36-p, S269-p Activation
SIK2 and SIK3 S413-pc Antagonizing Hpo pathway activity
LATS1/2(Wts) MST1/2 s909-p, T1079-pd Enzymatic activity
NUAK1  s464-p Protein stability
KIBRA T1079-pd Kinase activity
Itch Ubiquitination Protein degradation
CRL4DCAF1 Ubiquitination Protein degradation
LATS1 WWP1 Ubiquitination Protein degradation
Nedd4 Ubiquitination Protein degradation
LATS2 CHK1/2 S408-p Cell cycle regulation, apoptosis
SIAH1/2 Ubiquitination Protein degradation
Aurora A S83-p, S380-p Intracellular localization
MOB1A, MOB1B (Mats) MTS1/2 T12-p, T35-p, T74-p Molecular association
praja2 Ubiquitination Protein degradation
YAP (Yki) LATS1/2 S61-p, S109-p, S164-p The cytoplasmic retention
S127-p The binding of 14-3-3 
S397-pe Facilitates the binding of CK1δ/ε, leading to further serine phosphorylations
CK1ε/δ S400-p, S403-pf Generates a “phosphodegron” together with S397
c-Abl Y407-pg Promotes p73-dependent pro-apoptotic transcription
Src/YES1 Y407-p Induces assembly of the β-catenin–YAP complex
CDK1 T119-p, S289-p, S367-p Cell cycle regulation
NDR1/2 S127-p The cytoplasmic retention
JNK T119-p, S138-p, T154-p, S317-p, T362-p Inducing YAP to play dual role in different cell contexts
SCFβ-TRCP Ubiquitination Protein degradation
Fbxw7 Ubiquitination Protein degradation
Set7 K494-me Cytoplasmic retention
CBP/p300 K494-ac; K497-ac Altered nuclear activity
PML K97-sumo, K280-sumoh Stabilizes YAP1 by sumoylation and enhances p73-dependent transcription
TAZ LATS1/2 S66-p, S117-p Cytoplasmic retention
S89-p The binding of 14-3-3 
S311-p Facilitates the binding of CK1δ/ε, leading to further serine phosphorylations
GSK3-beta S58-p, S62-p Degradation
NEK1/CK1ε/δ S314-p Degradation/β-TrCP recruitment
c-Abl Y321-p Altered nuclear activity
PP1 S89-dep,S311-dep Promotes TAZ nuclear translocation, and stabilizes TAZ by disrupting the binding to the SCF E3 ubiquitin ligase
  1. The Hippo pathway acts primarily by inhibiting the nuclear functions of YAP and TAZ. Main PTMs of core components are described in Fig. 2; Table 1.)
  2. p phosphorylation; dep dephosphorylation; me methylation; ac acetylation; sumo sumoylation
  3. a T180-p in MST2
  4. b Tao1 phosphorylates T195-p of Hpo
  5. c Phosphorylation of Sav at Ser 413 in Drosophila
  6. d Thr1079 in Lats1 and Thr1041 in Lats2
  7. e S381 of YAP1 iso2 corresponds to S397 of YAP1
  8. f S384, S387 of YAP1 iso2 corresponds to S400, S403 of YAP1
  9. g Y357 of YAP1 iso3 corresponds to S407 of YAP1
  10. h K242 of YAP1 iso3 corresponds to K280 of YAP1