Biology:Pib2

From HandWiki
Short description: Yeast protein
Phosphatidylinositol 3-phosphate-binding protein 2
Identifiers
OrganismSaccharomyces cerevisiae
SymbolPIB2
Entrez852861
HomoloGene39059
RefSeq (mRNA)NM_001180888.3
RefSeq (Prot)NP_011492.3
UniProtP53191
Other data
ChromosomeVII: 0.45 - 0.45 Mb

Phosphatidylinositol 3-phosphate-binding protein 2 (Pib2) is a yeast protein involved in the regulation of TORC1 signaling[1][2][3][4][5] and lysosomal membrane permeabilization.[1] It is essential for the reactivation of TORC1 following exposure to rapamycin or nutrient starvation.[1][2][3][4]

Discovery

Pib2 was first identified as a FYVE domain-containing protein able to bind phosphatidylinositol 3-phosphate (PI3P).[6] Pib2 was later identified in a screen for rapamycin sensitivity, along with several other TORC1 regulatory proteins (including Ego1, Gtr1, Gtr2, and other key TORC1 related proteins).[7]

Structure

Pib2 is a 70.6 kDa protein with 635 amino acids (Uniprot - P53191). Pib2 has 5 weakly conserved motifs among fungi and 2 universally conserved motifs.[1] The partially conserved motifs are found in the N-terminal region of the protein and are generally referred to as regions A-E[1][4] The universally conserved motifs include a phosphatidylinositol-3-phosphate (PI3P)-binding FYVE domain, and a short tail motif at the C-terminus.[1]

Mammalian homologs

Pib2 has 2 mammalian homologs, Phafin1 (also known as LAPF or PLEKHF1) and Phafin2 (EAPF or PLEKHF2). The phafin proteins each have a PH (pleckstrin homology) domain and FYVE domain.[1] Phafin1 also has a tail motif similar to that of Pib2.[1] These proteins have not been shown to be involved in the regulation of mammalian TORC1 signaling but have been shown to be involved in related processes.[8][9]

Function

TORC1 regulation

In Saccharomyces cerevisiae, Pib2 has been shown to be involved in regulating TORC1 signaling.[1][2][3][4][5] Pib2 is found at the yeast vacuole and endosomes.[1][10] The PI3P binding FYVE domain of Pib2 is key for this localization.[1][3] Pib2 also interacts with some TORC1 components, including Kog1 and Tor1,[1][3][4][5] and has been shown to be necessary for TORC1 reactivation following inhibition by rapamycin or nutrient starvation.[1][2][3][4] Additionally, Pib2 is essential for TORC1 reactivation by stimulation with leucine and glutamine.[2][4]

In terms of TORC1 reactivation, it has been observed that Pib2 can have both a positive and negative effect. The C-terminus of Pib2 is key for TORC1 reactivation, whereas the N-terminal region has an inhibitory effect on TORC1 reactivation.[1][3]

Lysosomal membrane permeabilization

Lysosomal membrane permeabilization (LMP) is a process which is important for inducing cell death in a range of animals and plants.[1][11][12][13][14] LMP also occurs in Saccharomyces cerevisiae during sporulation.[15] Pib2 has been implicated in the regulation of this process in stressed yeast through the promotion of TORC1 activity.[1]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 "A LAPF/phafin1-like protein regulates TORC1 and lysosomal membrane permeabilization in response to endoplasmic reticulum membrane stress". Molecular Biology of the Cell 26 (25): 4631–45. December 2015. doi:10.1091/mbc.E15-08-0581. PMID 26510498. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 "Pib2 and the EGO complex are both required for activation of TORC1". Journal of Cell Science 130 (22): 3878–3890. November 2017. doi:10.1242/jcs.207910. PMID 28993463. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Functional mapping of yeast genomes by saturated transposition". eLife 6: e23570. May 2017. doi:10.7554/eLife.23570. PMID 28481201. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 "Gtr/Ego-independent TORC1 activation is achieved through a glutamine-sensitive interaction with Pib2 on the vacuolar membrane". PLOS Genetics 14 (4): e1007334. April 2018. doi:10.1371/journal.pgen.1007334. PMID 29698392. 
  5. ↑ 5.0 5.1 5.2 "Multilayered regulation of TORC1-body formation in budding yeast". Molecular Biology of the Cell 30 (3): 400–410. February 2019. doi:10.1091/mbc.E18-05-0297. PMID 30485160. 
  6. ↑ "FYVE domain targets Pib1p ubiquitin ligase to endosome and vacuolar membranes". The Journal of Biological Chemistry 276 (44): 41388–93. November 2001. doi:10.1074/jbc.M105665200. PMID 11526110. 
  7. ↑ "Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways". Nature Biotechnology 22 (1): 62–9. January 2004. doi:10.1038/nbt919. PMID 14661025. 
  8. ↑ "The lysosome-associated apoptosis-inducing protein containing the pleckstrin homology (PH) and FYVE domains (LAPF), representative of a novel family of PH and FYVE domain-containing proteins, induces caspase-independent apoptosis via the lysosomal-mitochondrial pathway". The Journal of Biological Chemistry 280 (49): 40985–95. December 2005. doi:10.1074/jbc.m502190200. PMID 16188880. 
  9. ↑ "Lysosomal interaction of Akt with Phafin2: a critical step in the induction of autophagy". PLOS ONE 9 (1): e79795. 2014-01-08. doi:10.1371/journal.pone.0079795. PMID 24416124. Bibcode: 2014PLoSO...979795M. 
  10. ↑ "Spatially Distinct Pools of TORC1 Balance Protein Homeostasis". Molecular Cell 73 (2): 325–338.e8. January 2019. doi:10.1016/j.molcel.2018.10.040. PMID 30527664. 
  11. ↑ "Lysosomal membrane permeabilization in cell death". Oncogene 27 (50): 6434–51. October 2008. doi:10.1038/onc.2008.310. PMID 18955971. 
  12. ↑ "Lysosomal proteins in cell death and autophagy". The FEBS Journal 282 (10): 1858–70. May 2015. doi:10.1111/febs.13253. PMID 25735653. 
  13. ↑ "Classes of programmed cell death in plants, compared to those in animals". Journal of Experimental Botany 62 (14): 4749–61. October 2011. doi:10.1093/jxb/err196. PMID 21778180. 
  14. ↑ "Vacuolar processing enzyme in plant programmed cell death". Frontiers in Plant Science 6: 234. 2015. doi:10.3389/fpls.2015.00234. PMID 25914711. 
  15. ↑ "Programmed nuclear destruction in yeast: self-eating by vacuolar lysis". Autophagy 9 (2): 263–5. February 2013. doi:10.4161/auto.22881. PMID 23187615. 



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