pha-4

Symbol: pha-4
Name: defective PHArynx development 4
Entrez gene ID: 180357
Ensembl gene ID: F38A6.1
Species: Worm (Taxid: 6239)

Functional description:
Acts as a transcription factor required for formation of the pharyngeal primordium. Binds to the consensus sequence 5'- T[AG]TT[TG][AG][TC]-3' with variations of the sequence affecting onset of target gene expression. Activates a wide array of pharyngeal genes including ceh-22 and myo-2 and represses ectodermal genes lin-26 and elt-3, ensuring pharyngeal cell fate. Required for recruitment of htz-1 to a subset of pharyngeal promoters to ensure gene activation and also acts synergistically with tbx-2 in pharyngeal development. Acts in the regulation of diet-restriction-mediated longevity by increasing expression of sod-1, sod-2, sod-4 and sod-5 but not sod-3. [UniProt]

Observation:

pha-4 is required for multiple forms of DR. RNAi of pha-4 completely cancels out the lifespan extension of eat-2 mutation. Mutants of pha-4 do not respond to bacterial DR. Therefore, loss of pha-4 completely blocks the response to varying food concentration. Moreover, pha-4 expression is increased in response to DR in wild-type. pha-4 overexpression increases longevity of wild-type only slightly, but significant that of daf-16 mutants. The response to DR involves the PHA-4-dependent expression of sod-1, sod-2 and sod-5. Reduction of pha-4 does not suppress the long lifespan of daf-2 mutants or animals with defective electron transport chain [17476212]. IF significantly extends lifespan of pha-4 [19079239]. sDR extends lifespan of mutants with a temperature sensitive allele of pha-4 or pha-4 RNAi knockdown, but not daf-16 RNAi [19239417]. PHA-4 may play a role in the life-extending effects of dietary restriction. RNAi of pha-4 decreases lifespan of wild-type worms, but not of daf-2 mutants or of animals with defective electron transport chains.



Interventions:
  • pha-4 mutation
  • pha-4 RNAi
  • pha-4 overexpression

  • Assays: Organismal Lifespan

    Classification:
  • Aging-Suppressor
  • Negative Aging-Suppressor
  • Positive Aging-Suppressor
  • DR-Essential


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • FOXA2 (9031)
  • pha-4 (6239)

  • Orthologs
  • FOXA1 (9606)
  • FOXA2 (9606)
  • FOXA3 (9606)
  • FOXA3 (9544)
  • Foxa1 (10116)
  • Foxa2 (10116)
  • Foxa3 (10116)
  • Foxa1 (10090)
  • Foxa2 (10090)
  • Foxa3 (10090)
  • FOXA1 (9544)
  • FOXA2 (9544)
  • fkh (7227)
  • FOXA1 (9606)
  • FOXA2 (9606)
  • FOXA3 (9606)
  • FOXA3 (9544)
  • lin-31 (6239)
  • Foxa1 (10116)
  • Foxa2 (10116)
  • Foxa3 (10116)
  • Foxa1 (10090)
  • Foxa2 (10090)
  • Foxa3 (10090)
  • FOXA1 (9544)
  • FOXA2 (9544)
  • fkh (7227)



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