PNC1

Symbol: PNC1
Name: Pyrazinamidase/NiCotinamidase 1
Entrez gene ID: 852846
Ensembl gene ID: YGL037C
Species: Yeast (Taxid: 4932)

Functional description:
Pnc1p; Nicotinamidase that converts nicotinamide to nicotinic acid as part of the NAD(+) salvage pathway, required for life span extension by calorie restriction; PNC1 expression responds to all known stimuli that extend replicative life span [Source:SGD;Acc:S000003005] [Ensembl]

Observation:

Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. PNC1 is upregulated under glucose DR [12736687]. Pnc1 reduces cellular nicotinamide levels, a product and noncompetitive inhibitor of Sir2 deacetylation reaction. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. Pnc1 catalyses the breakdown of nicotinamide to nicotinate and ammonia [12736687]. Deletion of PNC1 shortens replicative lifespan approximately by 10% [12736687] and largely prevents replicative lifespan extension of 0.5% glucose restriction. 0.5% glucose restriction slightly extends median replicative lifespan (by 10 - 15%) but not maximum replicative lifespan in pnc1Delta [14724176]. PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression [14729974]. Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain [12736687]. PNC1 deletion decreases chronological lifespan [17110466].



Interventions:
  • PNC1 overexpression +70%
  • PNC1 deletion -10%

  • Assays: Replicative Lifespan Chronological Lifespan

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


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • CG31216 (7227)
  • AgaP_AGAP001435 (7165)
  • pnc-2 (6239)
  • pnc-1 (6239)
  • SPBC365.20c (4896)
  • PNC1 (4932)
  • KLLA0F22242g (28985)
  • AGOS_AFR466C (33169)
  • GeneID:2679961 (148305)
  • NCU00713 (5141)

  • Orthologs
  • pnc-1 (6239)
  • pnc-2 (6239)
  • SPBC365.20c (4896)
  • Naam (7227)
  • pnc-1 (6239)
  • pnc-2 (6239)
  • SPBC365.20c (4896)
  • Naam (7227)
  • pnc-1 (6239)
  • pnc-2 (6239)
  • SPBC365.20c (4896)
  • Naam (7227)

  • Note: Reduce redundancy in the individual statements. Aging Interaction DB says 80% longer lifespan for Anderson 2003. Also it says: Overexpression of PNC1 decreases rDNA silencing. Which does not make sense.

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