Protein SQSTM1 map

Identifiers
HUGO:SQSTM1
sequestosome 1
HUGO:SQSTM1 HGNC:11280 ENTREZ:8878 UNIPROT:Q13501

Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
 Cancer Associated Fibroblasts  map  / CAF_INHIBITION_ANTITUMOR  map
 Cancer Associated Fibroblasts  map  / METABOLIC  map
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death  map  / STARVATION_AUTOPHAGY  map
 Regulated Cell Death  map  / CASPASES  map
 Regulated Cell Death  map  / DEATH_RECEPTOR_PATHWAYS  map
 Regulated Cell Death  map  / DEPENDANCE_RECEPTORS  map
 Regulated Cell Death  map  / FAS_RESPONSE  map
 Regulated Cell Death  map  / TRAIL_RESPONSE  map
 Regulated Cell Death  map  / ER_STRESS  map
 Regulated Cell Death  map  / FERROPTOSIS  map

References
PMID:25002027
SQSTM1 (p62) p62 is a suppressor of inflammation and the CAF phenotype in the tumor microenvironment
p62 controls IL-6 levels by repressing ROS production through metabolic reprogramming
We found significantly reduced levels of c-Myc in p62 KO fibroblasts as well as in WT fibroblasts in which p62 has been knocked down by shRNA
reduction in GLUT1 levels in p62-deficient fibroblasts.
We also observed a decrease in the direct conversion of [U-13C5] glutamine to glutamate in p62 KO fibroblasts, with a relative increase in the fraction of glutamate derived from [1,2-13C2]glucose
and reduced levels of the glutamine transporters SLC7A5 and SLC1A5, as well as glutaminase-1 (GLS1) (Figure 4O), a critical enzyme in the pathway that catalyzes the conversion of glutamine into glutamate
p62 KO cells exhibited decreased glucose uptake and lactate secretion
p62 KO cells displayed reduced mTORC1 activity
mTORC1 activity in p62 KO fibroblasts accounts for the low levels of c-Myc and the subsequent increase in IL-6 production in these mutant cells. Treatment of WT fibroblasts with rapamycin or Torin, two different inhibitors of mTORC1, effectively reduced c-Myc levels
We found significantly reduced levels of c-Myc in p62 KO fibroblasts as well as in WT fibroblasts in which p62 has been knocked down by shRNA (Figures 5A and 5B), and a reduction in the levels of the key glutamine transporters SLC7A5 and SLC1A5, and GLS1 (Figure 4O), which are targets of c-Myc (Dang, 2012). Interestingly, ectopic expression of c-Myc in p62 KO fibroblasts (Figure 5C) reverted the p62-deficient phenotype in terms of IL-6 production
PMID:21981924
p62 is a key regulator of nutrient sensing in the mTORC1 pathway (data is not from fibroblasts).
PMID:26587781
Sequestosme 1, p62
PMID:20531300
PMID:16252010
PMID:15340068
Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation.PMID:19450509
polyubiquitination of caspase-8, rather than targeting it for proteasomal degradation, is critical for sustaining caspase-8 activity after dissociation from the DISC
PMID:28574505

SQSTM1@Endosome

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death  map  / STARVATION_AUTOPHAGY  map
 Regulated Cell Death  map  / CASPASES  map
 Regulated Cell Death  map  / DEATH_RECEPTOR_PATHWAYS  map
 Regulated Cell Death  map  / DEPENDANCE_RECEPTORS  map
 Regulated Cell Death  map  / FAS_RESPONSE  map
 Regulated Cell Death  map  / TRAIL_RESPONSE  map

References
rc_re1674( Regulated Cell Death  map ):
Apoptosis complex led by FAS ligation
PMID:12702723
PMID:9184224
PMID:23069999
PMID:16498403
caspase-8 formed triple complex with TRAF2 and FLASH. Taken together, these results suggest that endogenous caspase-8 mediates TNF-alpha-induced activation of NF-kappaB via FLASH

Modifications:
In compartment: Cytosol
  1. SQSTM1@Cytosol map
In compartment: Endosome
  1. SQSTM1@Endosome map
In compartment: Ubiquitinated cargos
  1. SQSTM1|​pho|​ubi@Ubiquitinated cargos map
  2. SQSTM1|​pho|​pho|​ubi@Ubiquitinated cargos map
Participates in complexes:
In compartment: Autopagosome
  1. LC3-I*:​SQSTM1@Autopagosome map
  2. Caspase8,10*|​ubi:​LC3-I*:​SQSTM1@Autopagosome map
In compartment: Cytosol
  1. NRIF*|​ubi:​SQSTM1:​TRAF6@Cytosol map
In compartment: Nucleus
  1. NRIF*|​ubi:​SQSTM1@Nucleus map
In compartment: Ubiquitinated cargos
  1. KEAP1:​SQSTM1|​pho|​pho|​ubi@Ubiquitinated cargos map
Participates in reactions:
As Reactant or Product:
  1. SQSTM1@Cytosol map → map NEGATIVE_REGULATORS OF_CAF@Cytosol map
  2. SQSTM1@Cytosol map → map ROS production@Cytosol map
  3. SQSTM1@Cytosol map + NRIF*|​ubi@Cytosol map + TRAF6@Cytosol map → map NRIF*|​ubi:​SQSTM1:​TRAF6@Cytosol map
  4. NRIF*|​ubi:​SQSTM1:​TRAF6@Cytosol map → map NRIF*|​ubi:​SQSTM1@Nucleus map
  5. SQSTM1@Cytosol map + LC3-I*@Autopagosome map → map LC3-I*:​SQSTM1@Autopagosome map
  6. LC3-I*:​SQSTM1@Autopagosome map + Caspase8,10*|​ubi|​active@Cytosol map → map Caspase8,10*|​ubi:​LC3-I*:​SQSTM1@Autopagosome map
  7. SQSTM1@Cytosol map → map SQSTM1|​pho|​ubi@Ubiquitinated cargos map
  8. SQSTM1|​pho|​pho|​ubi@Ubiquitinated cargos map + KEAP1@Cytosol map → map KEAP1:​SQSTM1|​pho|​pho|​ubi@Ubiquitinated cargos map
  9. SQSTM1|​pho|​ubi@Ubiquitinated cargos map → map SQSTM1|​pho|​pho|​ubi@Ubiquitinated cargos map
  10. KEAP1:​SQSTM1|​pho|​pho|​ubi@Ubiquitinated cargos map → map degraded
As Catalyser:
  1. gSLC2A1@Cytosol map → map rSLC2A1@Cytosol map
  2. DEPTOR:​MLST8:​MTOR:​PRAS40*:​RPTOR@Cytosol map → map (DEPTOR:​MLST8:​MTOR|​pho:​PRAS40*:​RPTOR)|​active@Cytosol map
  3. glutamine@Cytosol map → map Glutamate@Cytosol map
  4. CUL3:​Caspase8,10*|​ubi:​DR4/5*|​gly|​pal:​RBX1@Cytosol map → map rc_s6308
  5. FASLG:​FAS|​pal@Cytosol map + Caspase8,10*:​FLASH*@Cytosol map + FAF1@Cytosol map + FADD@Cytosol map + DAXX@Cytosol map + RIPK1@Cytosol map → map Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1@Endosome map
  6. Caspase8*@Cytosol map → map cleaved~Caspase8*@Cytosol map
  7. Caspase10*@Cytosol map → map cleaved Caspase 10*@Cytosol map
  8. Mitochondrial Membrane ubiquitinylation@Cytosol map → map Mitophagy@Cytosol map