Molecule Information

General Information of the Molecule (ID: Mol04441)

• Name: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) ,Homo sapiens
• Synonyms: Ligand effect modulator 6
• Molecule Type: Protein
• Gene Name: PPARGC1A
• Gene ID: 10891
• Sequence:
  MAWDMCNQDSESVWSDIECAALVGEDQPLCPDLPELDLSELDVNDLDTDSFLGGLKWCSD
  QSEIISNQYNNEPSNIFEKIDEENEANLLAVLTETLDSLPVDEDGLPSFDALTDGDVTT
  D NEASPSSMPDGTPPPQEAEEPSLLKKLLLAPANTQLSYNECSGLSTQNHANHNHRIRT
  NP AIVKTENSWSNKAKSICQQQKPQRRPCSELLKYLTTNDDPPHTKPTENRNSSRDKCT
  SKK KSHTQSQSQHLQAKPTTLSLPLTPESPNDPKGSPFENKTIERTLSVELSGTAGLTP
  PTTP PHKANQDNPFRASPKLKSSCKTVVPPPSKKPRYSESSGTQGNNSTKKGPEQSELY
  AQLSK SSVLTGGHEERKTKRPSLRLFGDHDYCQSINSKTEILINISQELQDSRQLENKD
  VSSDWQ GQICSSTDSDQCYLRETLEASKQVSPCSTRKQLQDQEIRAELNKHFGHPSQAV
  FDDEADK TGELRDSDFSNEQFSKLPMFINSGLAMDGLFDDSEDESDKLSYPWDGTQSYS
  LFNVSPSC SSFNSPCRDSVSPPKSLFSQRPQRMRSRSRSFSRHRSCSRSPYSRSRSRSP
  GSRSSSRSC YYYESSHYRHRTHRNSPLYVRSRSRSPYSRRPRYDSYEEYQHERLKREEY
  RREYEKRESE RAKQRERQRQKAIEERRVIYVGKIRPDTTRTELRDRFEVFGEIEECTVN
  LRDDGDSYGFI TYRYTCDAFAALENGYTLRRSNETDFELYFCGRKQFFKSNYADLDSNS
  DDFDPASTKSKY DSLDFDSLLKEAQRSLRR
• Function: Transcriptional coactivator for steroid receptors and nuclearreceptors . Greatly increases thetranscriptional activity of PPARG and thyroid hormone receptor on theuncoupling protein promoter . Can regulate key mitochondrial genes that contributeto the program of adaptive thermogenesis . Plays an essential role in metabolicreprogramming in response to dietary availability through coordinationof the expression of a wide array of genes involved in glucose andfatty acid metabolism . Acts as a key regulator of gluconeogenesis:stimulates hepatic gluconeogenesis by increasing the expression ofgluconeogenic enzymes, and acting together with FOXO1 to promote thefasting gluconeogenic program .Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner . Also involved in the integration ofthe circadian rhythms and energy metabolism . Requiredfor oscillatory expression of clock genes, such as BMAL1 and NR1D1,through the coactivation of RORA and RORC, and metabolic genes, such asPDK4 and PEPCK . {ECO:0000250|UniProtKB:O70343,ECO:0000269|PubMed:10713165, ECO:0000269|PubMed:16753578,ECO:0000269|PubMed:20005308, ECO:0000269|PubMed:21376232,ECO:0000269|PubMed:23142079, ECO:0000269|PubMed:23836911,ECO:0000269|PubMed:28363985, ECO:0000269|PubMed:32433991}.
• Uniprot ID: PRGC1_HUMAN
• Ensembl ID: ENSG000001098199
• HGNC ID: HGNC:9237

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 22Rv-1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: Flow cytometric assay
• Mechanism Description: This research demonstrated that ANGPTL4 is primarily expressed in CAFs and that ANGPTL4 can bind to IQGAP1 on the PCa cell membrane, activating the Raf-MEK-ERK-PGC1 pathway. This process promotes mitochondrial biogenesis and OXPHOS function, ultimately leading to growth and chemoresistance in PCa.

References

• Ref 1: Cancer-associated fibroblasts regulate mitochondrial metabolism and inhibit chemosensitivity via ANGPTL4-IQGAP1 axis in prostate cancer. J Adv Res. 2024 Dec 6:S2090-1232(24)00559-9.