Molecule Information

General Information of the Molecule (ID: Mol04063)

• Name: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) ,Homo sapiens
• Synonyms: Ligand effect modulator 6
• Molecule Type: Protein
• Gene Name: PPARGC1A
• Gene ID: 10891
• Location: chr4:23755041-23904089[-]
• Sequence:
  MAWDMCNQDSESVWSDIECAALVGEDQPLCPDLPELDLSELDVNDLDTDSFLGGLKWCSD
  QSEIISNQYNNEPSNIFEKIDEENEANLLAVLTETLDSLPVDEDGLPSFDALTDGDVTTD
  NEASPSSMPDGTPPPQEAEEPSLLKKLLLAPANTQLSYNECSGLSTQNHANHNHRIRTNP
  AIVKTENSWSNKAKSICQQQKPQRRPCSELLKYLTTNDDPPHTKPTENRNSSRDKCTSKK
  KSHTQSQSQHLQAKPTTLSLPLTPESPNDPKGSPFENKTIERTLSVELSGTAGLTPPTTP
  PHKANQDNPFRASPKLKSSCKTVVPPPSKKPRYSESSGTQGNNSTKKGPEQSELYAQLSK
  SSVLTGGHEERKTKRPSLRLFGDHDYCQSINSKTEILINISQELQDSRQLENKDVSSDWQ
  GQICSSTDSDQCYLRETLEASKQVSPCSTRKQLQDQEIRAELNKHFGHPSQAVFDDEADK
  TGELRDSDFSNEQFSKLPMFINSGLAMDGLFDDSEDESDKLSYPWDGTQSYSLFNVSPSC
  SSFNSPCRDSVSPPKSLFSQRPQRMRSRSRSFSRHRSCSRSPYSRSRSRSPGSRSSSRSC
  YYYESSHYRHRTHRNSPLYVRSRSRSPYSRRPRYDSYEEYQHERLKREEYRREYEKRESE
  RAKQRERQRQKAIEERRVIYVGKIRPDTTRTELRDRFEVFGEIEECTVNLRDDGDSYGFI
  TYRYTCDAFAALENGYTLRRSNETDFELYFCGRKQFFKSNYADLDSNSDDFDPASTKSKY
  DSLDFDSLLKEAQRSLRR
• 3D-structure: PDB ID: 6W9L; Classification: Hormone; Method: X-ray diffraction; Resolution: 1.45 Å
• Function: Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter (PubMed:10713165, PubMed:20005308, PubMed:21376232). Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis (PubMed:10713165, PubMed:20005308, PubMed:21376232). Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism (PubMed:10713165, PubMed:20005308, PubMed:21376232). Acts as a key regulator of gluconeogenesis: stimulates hepatic gluconeogenesis by increasing the expression of gluconeogenic enzymes, and acting together with FOXO1 to promote the fasting gluconeogenic program (PubMed:16753578, PubMed:23142079). Induces the expression of PERM1 in the skeletal muscle in an ESRRA- dependent manner (PubMed:23836911). Also involved in the integration of the circadian rhythms and energy metabolism (By similarity). Required for oscillatory expression of clock genes, such as BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK (By similarity). .
• Uniprot ID: PRGC1_HUMAN
• Ensembl ID: ENSG00000109819
• 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

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

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

Sunitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Specifically, overexpression of MIER2 plays a pivotal role in enhancing lipid accumulation, promoting malignancy, and contributing to sunitinib resistance in RCC. This occurs through thedownregulationof PGC1A via the MIER2/HDAC1/P53 axis. Our findings highlight the potential significance of targeting HDAC1, and we propose that TSA, an HDAC2 inhibitor, may serve as a promising therapeutic compound for patients with sunitinib-resistant advanced RCC.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: OS-RC-2 cells; Kidney; Homo sapiens (Human); CVCL_E313
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Specifically, overexpression of MIER2 plays a pivotal role in enhancing lipid accumulation, promoting malignancy, and contributing to sunitinib resistance in RCC. This occurs through thedownregulationof PGC1A via the MIER2/HDAC1/P53 axis. Our findings highlight the potential significance of targeting HDAC1, and we propose that TSA, an HDAC4 inhibitor, may serve as a promising therapeutic compound for patients with sunitinib-resistant advanced RCC.

References

• Ref 1: MIER2/PGC1A elicits sunitinib resistance via lipid metabolism in renal cell carcinoma. J Adv Res. 2025 Apr;70:287-305.