Pib2

From Wikipedia the free encyclopedia

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
Search for
StructuresSwiss-model
DomainsInterPro

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[edit]

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[edit]

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[edit]

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[edit]

TORC1 regulation[edit]

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[edit]

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[edit]

  1. ^ a b c d e f g h i j k l m n o p Kim A, Cunningham KW (December 2015). Glick BS (ed.). "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. doi:10.1091/mbc.E15-08-0581. PMC 4678020. PMID 26510498.
  2. ^ a b c d e Varlakhanova NV, Mihalevic MJ, Bernstein KA, Ford MG (November 2017). "Pib2 and the EGO complex are both required for activation of TORC1". Journal of Cell Science. 130 (22): 3878–3890. doi:10.1242/jcs.207910. PMC 5702048. PMID 28993463.
  3. ^ a b c d e f g Michel AH, Hatakeyama R, Kimmig P, Arter M, Peter M, Matos J, et al. (May 2017). "Functional mapping of yeast genomes by saturated transposition". eLife. 6: e23570. doi:10.7554/eLife.23570. PMC 5466422. PMID 28481201.
  4. ^ a b c d e f g Ukai H, Araki Y, Kira S, Oikawa Y, May AI, Noda T (April 2018). "Gtr/Ego-independent TORC1 activation is achieved through a glutamine-sensitive interaction with Pib2 on the vacuolar membrane". PLOS Genetics. 14 (4): e1007334. doi:10.1371/journal.pgen.1007334. PMC 5919408. PMID 29698392.
  5. ^ a b c Sullivan A, Wallace RL, Wellington R, Luo X, Capaldi AP (February 2019). Luo K (ed.). "Multilayered regulation of TORC1-body formation in budding yeast". Molecular Biology of the Cell. 30 (3): 400–410. doi:10.1091/mbc.E18-05-0297. PMC 6589571. PMID 30485160.
  6. ^ Shin ME, Ogburn KD, Varban OA, Gilbert PM, Burd CG (November 2001). "FYVE domain targets Pib1p ubiquitin ligase to endosome and vacuolar membranes". The Journal of Biological Chemistry. 276 (44): 41388–93. doi:10.1074/jbc.M105665200. PMID 11526110. S2CID 19257611.
  7. ^ Parsons AB, Brost RL, Ding H, Li Z, Zhang C, Sheikh B, et al. (January 2004). "Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways". Nature Biotechnology. 22 (1): 62–9. doi:10.1038/nbt919. PMID 14661025. S2CID 10606058.
  8. ^ Chen W, Li N, Chen T, Han Y, Li C, Wang Y, et al. (December 2005). "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. doi:10.1074/jbc.m502190200. PMID 16188880. S2CID 13634278.
  9. ^ Matsuda-Lennikov M, Suizu F, Hirata N, Hashimoto M, Kimura K, Nagamine T, et al. (2014-01-08). Chiorini JA (ed.). "Lysosomal interaction of Akt with Phafin2: a critical step in the induction of autophagy". PLOS ONE. 9 (1): e79795. Bibcode:2014PLoSO...979795M. doi:10.1371/journal.pone.0079795. PMC 3885392. PMID 24416124.
  10. ^ Hatakeyama R, Péli-Gulli MP, Hu Z, Jaquenoud M, Garcia Osuna GM, Sardu A, et al. (January 2019). "Spatially Distinct Pools of TORC1 Balance Protein Homeostasis". Molecular Cell. 73 (2): 325–338.e8. doi:10.1016/j.molcel.2018.10.040. PMID 30527664.
  11. ^ Boya P, Kroemer G (October 2008). "Lysosomal membrane permeabilization in cell death". Oncogene. 27 (50): 6434–51. doi:10.1038/onc.2008.310. hdl:10261/59040. PMID 18955971. S2CID 21635483.
  12. ^ Mrschtik M, Ryan KM (May 2015). "Lysosomal proteins in cell death and autophagy". The FEBS Journal. 282 (10): 1858–70. doi:10.1111/febs.13253. PMID 25735653. S2CID 11609431.
  13. ^ van Doorn WG (October 2011). "Classes of programmed cell death in plants, compared to those in animals". Journal of Experimental Botany. 62 (14): 4749–61. doi:10.1093/jxb/err196. PMID 21778180.
  14. ^ Hatsugai N, Yamada K, Goto-Yamada S, Hara-Nishimura I (2015). "Vacuolar processing enzyme in plant programmed cell death". Frontiers in Plant Science. 6: 234. doi:10.3389/fpls.2015.00234. PMC 4390986. PMID 25914711.
  15. ^ Eastwood MD, Cheung SW, Meneghini MD (February 2013). "Programmed nuclear destruction in yeast: self-eating by vacuolar lysis". Autophagy. 9 (2): 263–5. doi:10.4161/auto.22881. PMC 3552897. PMID 23187615.
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