Abstract 4195: Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E-BP1

2012 ◽  
Author(s):  
Jianyu Liu ◽  
Tianyan Gao
Keyword(s):  
Cell Growth ◽  
Protein Phosphatase ◽  
Protein Translation

scholarly journals Protein Phosphatase PPM1G Regulates Protein Translation and Cell Growth by Dephosphorylating 4E Binding Protein 1 (4E-BP1)

2013 ◽  
Vol 288 (32) ◽  
pp. 23225-23233 ◽  
Author(s):  
Jianyu Liu ◽  
Payton D. Stevens ◽  
Nichole E. Eshleman ◽  
Tianyan Gao
Keyword(s):  
Cell Growth ◽  
Protein Phosphatase ◽  
Binding Protein ◽  
Protein Translation

scholarly journals The EGP1 gene may be a positive regulator of protein phosphatase type 1 in the growth control of Saccharomyces cerevisiae.

1995 ◽  
Vol 15 (7) ◽  
pp. 3767-3776 ◽  
Author(s):  
N Hisamoto ◽  
D L Frederick ◽  
K Sugimoto ◽  
K Tatchell ◽  
K Matsumoto
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Growth ◽  
Protein Phosphatase ◽  
Double Mutant ◽  
Growth Control ◽  
Restrictive Temperature ◽  
Extra Copy ◽  
Additional Gene ◽  
Positive Modulator

The Saccharomyces cerevisiae GLC7 gene encodes the catalytic subunit of type 1 protein phosphatase (PP1) and is required for cell growth. A cold-sensitive glc7 mutant (glc7Y170) arrests in G2/M but remains viable at the restrictive temperature. In an effort to identify additional gene products that function in concert with PP1 to regulate growth, we isolated a mutation (gpp1) that exacerbated the growth phenotype of the glc7Y170 mutation, resulting in rapid death of the double mutant at the nonpermissive temperature. We identified an additional gene, EGP1, as an extra-copy suppressor of the glc7Y170 gpp1-1 double mutant. The nucleotide sequence of EGP1 predicts a leucine-rich repeat protein that is similar to Sds22, a protein from the fission yeast Schizosaccharomyces pombe that positively modulates PP1. EGP1 is essential for cell growth but becomes dispensable upon overexpression of the GLC7 gene. Egp1 and PP1 directly interact, as assayed by coimmunoprecipitation. These results suggest that Egp1 functions as a positive modulator of PP1 in the growth control of S. cerevisiae.

scholarly journals Nutrient-responsive mTOR signalling grows on Sterile ground

2007 ◽  
Vol 403 (1) ◽  
Author(s):  
Simon J. Cook ◽  
Simon J. Morley
Keyword(s):  
Amino Acids ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cell Growth ◽  
Cell Size ◽  
Protein Translation ◽  
Small Gtpase ◽  
Mtor Activity ◽  
Mtor Signalling

The control of cell growth, that is cell size, is largely controlled by mTOR (the mammalian target of rapamycin), a large serine/threonine protein kinase that regulates ribosome biogenesis and protein translation. mTOR activity is regulated both by the availability of growth factors, such as insulin/IGF-1 (insulin-like growth factor 1), and by nutrients, notably the supply of certain key amino acids. The last few years have seen a remarkable increase in our understanding of the canonical, growth factor-regulated pathway for mTOR activation, which is mediated by the class I PI3Ks (phosphoinositide 3-kinases), PKB (protein kinase B), TSC1/2 (the tuberous sclerosis complex) and the small GTPase, Rheb. However, the nutrient-responsive input into mTOR is important in its own right and is also required for maximal activation of mTOR signalling by growth factors. Despite this, the details of the nutrient-responsive signalling pathway(s) controlling mTOR have remained elusive, although recent studies have suggested a role for the class III PI3K hVps34. In this issue of the Biochemical Journal, Findlay et al. demonstrate that the protein kinase MAP4K3 [mitogen-activated protein kinase kinase kinase kinase-3, a Ste20 family protein kinase also known as GLK (germinal centre-like kinase)] is a new component of the nutrient-responsive pathway. MAP4K3 activity is stimulated by administration of amino acids, but not growth factors, and this is insensitive to rapamycin, most likely placing MAP4K3 upstream of mTOR. Indeed, MAP4K3 is required for phosphorylation of known mTOR targets such as S6K1 (S6 kinase 1), and overexpression of MAP4K3 promotes the rapamycin-sensitive phosphorylation of these same targets. Finally, knockdown of MAP4K3 levels causes a decrease in cell size. The results suggest that MAP4K3 is a new component in the nutrient-responsive pathway for mTOR activation and reveal a completely new function for MAP4K3 in promoting cell growth. Given that mTOR activity is frequently deregulated in cancer, there is much interest in new strategies for inhibition of this pathway. In this context, MAP4K3 looks like an attractive drug target since inhibitors of this enzyme should switch off mTOR, thereby inhibiting cell growth and proliferation, and promoting apoptosis.

scholarly journals TOR Controls Transcriptional and Translational Programs via Sap-Sit4 Protein Phosphatase Signaling Effectors

2004 ◽  
Vol 24 (19) ◽  
pp. 8332-8341 ◽  
Author(s):  
John R. Rohde ◽  
Susan Campbell ◽  
Sara A. Zurita-Martinez ◽  
N. Shane Cutler ◽  
Mark Ashe ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Growth ◽  
Protein Phosphatase ◽  
Immunosuppressive Drug ◽  
Regulatory Proteins ◽  
Initiation Factor ◽  
Regulatory Subunit ◽  
Tor Signaling ◽  
Amino Acid Availability ◽  
Increased Sensitivity

ABSTRACT The Tor kinases are the targets of the immunosuppressive drug rapamycin and couple nutrient availability to cell growth. In the budding yeast Saccharomyces cerevisiae, the PP2A-related phosphatase Sit4 together with its regulatory subunit Tap42 mediates several Tor signaling events. Sit4 interacts with other potential regulatory proteins known as the Saps. Deletion of the SAP or SIT4 genes confers increased sensitivity to rapamycin and defects in expression of subsets of Tor-regulated genes. Sap155, Sap185, or Sap190 can restore these responses. Strains lacking Sap185 and Sap190 are hypersensitive to rapamycin, and this sensitivity is Gcn2 dependent and correlated with a defect in translation, constitutive eukaryotic initiation factor 2α hyperphosphorylation, induction of GCN4 translation, and hypersensitivity to amino acid starvation. We conclude that Tor signals via Sap-Sit4 complexes to control both transcriptional and translational programs that couple cell growth to amino acid availability.

The kinase triad, AMPK, mTORC1 and ULK1, maintains energy and nutrient homoeostasis

2013 ◽  
Vol 41 (4) ◽  
pp. 939-943 ◽  
Author(s):  
Elaine A. Dunlop ◽  
Andrew R. Tee
Keyword(s):  
Amino Acid ◽  
Cell Growth ◽  
Protein Kinases ◽  
Mammalian Target Of Rapamycin ◽  
Nutrient Status ◽  
Protein Translation ◽  
Cellular Growth ◽  
Target Of Rapamycin ◽  
Amp Activated Protein Kinase ◽  
Rate Limiting

In order for cells to divide in a proficient manner, they must first double their biomass, which is considered to be the main rate-limiting phase of cell proliferation. Cell growth requires an abundance of energy and biosynthetic precursors such as lipids and amino acids. Consequently, the energy and nutrient status of the cell is acutely monitored and carefully maintained. mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] is often considered to be the master regulator of cell growth that enhances cellular biomass through up-regulation of protein translation. In order for cells to control cellular homoeostasis during growth, there is close signalling interplay between mTORC1 and two other protein kinases, AMPK (AMP-activated protein kinase) and ULK1 (Unc-51-like kinase 1). This kinase triad collectively senses the energy and nutrient status of the cell and appropriately dictates whether the cell will actively favour energy- and amino-acid-consuming anabolic processes such as cellular growth, or energy- and amino-acid-generating catabolic processes such as autophagy. The present review discusses important feedback mechanisms between these three homoeostatic protein kinases that orchestrate cell growth and autophagy, with a particular focus on the mTORC1 component raptor (regulatory associated protein of mammalian target of rapamycin), as well as the autophagy-initiating kinase ULK1.

scholarly journals Control of cellular morphogenesis by the Ip12/Bem2 GTPase-activating protein: possible role of protein phosphorylation.

1994 ◽  
Vol 127 (5) ◽  
pp. 1381-1394 ◽  
Author(s):  
Y J Kim ◽  
L Francisco ◽  
G C Chen ◽  
E Marcotte ◽  
C S Chan
Keyword(s):  
Cell Growth ◽  
Protein Phosphorylation ◽  
Protein Phosphatase ◽  
Gene Dosage ◽  
Protein Domain ◽  
Gtpase Activating Protein ◽  
Synthetic Lethal ◽  
Lethal Phenotype ◽  
Polarized Cell Growth ◽  
Mutant Phenotypes

The IPL2 gene is known to be required for normal polarized cell growth in the budding yeast Saccharomyces cerevisiae. We now show that IPL2 is identical to the previously identified BEM2 gene. bem2 mutants are defective in bud site selection at 26 degrees C and localized cell surface growth and organization of the actin cytoskeleton at 37 degrees C. BEM2 encodes a protein with a COOH-terminal domain homologous to sequences found in several GTPase-activating proteins, including human Bcr. The GTPase-activating protein-domain from the Bem2 protein (Bem2p) or human Bcr can functionally substitute for Bem2p. The Rho1 and Rho2 GTPases are the likely in vivo targets of Bem2p because bem2 mutant phenotypes can be partially suppressed by increasing the gene dosage of RHO1 or RHO2. CDC55 encodes the putative regulatory B subunit of protein phosphatase 2A, and mutations in BEM2 have previously been identified as suppressors of the cdc55-1 mutation. We show here that mutations in the previously identified GRR1 gene can suppress bem2 mutations. grr1 and cdc55 mutants are both elongated in shape and cold-sensitive for growth, and cells lacking both GRR1 and CDC55 exhibit a synthetic lethal phenotype. bem2 mutant phenotypes also can be suppressed by the SSD1-vl (also known as SRK1) mutation, which was shown previously to suppress mutations in the protein phosphatase-encoding SIT4 gene. Cells lacking both BEM2 and SIT4 exhibit a synthetic lethal phenotype even in the presence of the SSD1-v1 suppressor. These genetic interactions together suggest that protein phosphorylation and dephosphorylation play an important role in the BEM2-mediated process of polarized cell growth.

scholarly journals Principles of cellular resource allocation revealed by condition-dependent proteome profiling

2017 ◽  
Author(s):  
Eyal Metzl-Raz ◽  
Moshe Kafri ◽  
Gilad Yaakov ◽  
Ilya Soifer ◽  
Yonat Gurvich ◽  
...  
Keyword(s):  
Growth Rate ◽  
Resource Allocation ◽  
Steady State ◽  
Cell Growth ◽  
Ribosomal Proteins ◽  
Budding Yeast ◽  
Protein Translation ◽  
Metabolic Rates ◽  
Proteome Profiling ◽  
State Growth

Growing cells coordinate protein translation with metabolic rates. Central to this coordination is ribosome production. Ribosomes drive cell growth, but translation of ribosomal proteins competes with production of other proteins. Theory shows that cell growth is maximized when all expressed ribosomes are constantly translating. To examine whether budding yeast function at this limit of full ribosomal usage, we profiled the proteomes of cells growing in different environments. We find that cells produce an excess of ribosomal proteins, amounting to a constant ≈8% of the proteome. Accordingly, ≈25% of ribosomal proteins expressed in rapidly growing cells do not contribute to translation. This fraction increases as growth rate decreases. These excess ribosomal proteins are employed during nutrient upshift or when forcing unneeded expression. We suggest that steadily growing cells prepare for conditions that demand increased translation by producing excess ribosomes, at the expense of lower steady-state growth rate.

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