The chaperone network connected to human ribosome-associated complex.
Mammalian ribosome-associated complex (mRAC), consisting of the J-domain protein MPP11 and the atypical Hsp70 homolog (70-homolog) Hsp70L1, can partly complement the function of RAC, which is the homologous complex from Saccharomyces cerevisiae. RAC is the J-domain partner exclusively of the 70-homolog Ssb, which directly and independently of RAC binds to the ribosome. We here show that growth defects due to mRAC depletion in HeLa cells resemble those of yeast strains lacking RAC. Functional conservation, however, did not extend to the 70-homolog partner of mRAC. None of the major human 70-homologs was able to complement the growth defects of yeast strains lacking Ssb or was bound to ribosomes in an Ssb-like manner. Instead, our data suggest that mRAC was a specific partner of human Hsp70 but not of its close homolog Hsc70. On a mechanistic level, ATP binding, but not ATP hydrolysis, by Hsp70L1 affected mRAC's function as a J-domain partner of Hsp70. The combined data indicate that, while functionally conserved, yeast and mammalian cells have evolved distinct solutions to ensure that Hsp70-type chaperones can efficiently assist the biogenesis of newly synthesized polypeptide chains.
Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, Stefan-Meier-Str. 17, D-79104 Freiburg, Germany.
Himjyot
H
Jaiswal
Charlotte
C
Conz
Hendrik
H
Otto
Tina
T
Wölfle
Edith
E
Fitzke
Matthias P
MP
Mayer
Sabine
S
Rospert
D000255:Adenosine Triphosphate / Q000378:metabolism; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; C414672:DNAJC2 protein, human; D018840:HSP70 Heat-Shock Proteins; C483693:Hspa14 protein, human; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4203-8
11929993
Biochemistry. 2006 Dec 19;45(50):15075-84
17154545
Development. 1999 Feb;126(4):649-58
9895313
Cell Mol Life Sci. 2005 Mar;62(6):670-84
15770419
Biochim Biophys Acta. 2010 Jun;1803(6):662-72
20226819
Biochim Biophys Acta. 1999 Jan 18;1444(1):138-42
9931472
Nucleic Acids Res. 1996 Jul 1;24(13):2519-24
8692690
PLoS Biol. 2008 Apr 8;6(4):e84
18399720
Science. 1990 May 18;248(4957):850-4
2188360
J Biol Chem. 2010 Jan 29;285(5):3227-34
19920147
Cancer Res. 2000 Oct 1;60(19):5529-35
11034098
Rev Physiol Biochem Pharmacol. 2005;155:1-30
15928926
EMBO J. 2006 Jun 7;25(11):2519-28
16688212
Mol Biol Cell. 2000 Mar;11(3):833-48
10712503
Cancer Res. 2001 Mar 15;61(6):2625-31
11289140
Curr Genomics. 2008;9(5):338-248
19471609
J Biol Chem. 2001 Aug 31;276(35):32538-44
11441021
J Biol Chem. 2007 Nov 23;282(47):33977-84
17901048
Mech Dev. 2009 Oct;126(10):842-51
19646527
Methods Enzymol. 1991;194:627-43
2005813
Science. 2005 May 13;308(5724):1032-4
15802566
RNA. 2003 Aug;9(8):1019-24
12869712
Biochem Biophys Res Commun. 2004 Nov 5;324(1):326-32
15465022
Eukaryot Cell. 2005 Jan;4(1):82-9
15643063
Cell Stress Chaperones. 2001 Jul;6(3):282-95
11599570
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3762-7
11274393
J Biol Chem. 2004 May 21;279(21):21992-2001
15028727
Genes Dev. 2009 Sep 1;23(17):2102-15
19723765
Ann N Y Acad Sci. 1999 Nov 28;884:99-109
10842587
Methods Enzymol. 1991;194:3-21
2005794
Cancer Res. 2009 Aug 1;69(15):6275-81
19584290
J Cell Physiol. 1981 Jan;106(1):41-7
6937470
Cell Stress Chaperones. 2009 Jan;14(1):105-11
18663603
Mol Biol Evol. 2001 Jul;18(7):1401-12
11420378
Nature. 1990 Aug 16;346(6285):623-8
2143562
Mol Cell Biochem. 2004 Oct;265(1-2):27-35
15543931
Mol Cell Biol. 2004 Oct;24(20):9186-97
15456889
EMBO Rep. 2003 Jun;4(6):609-15
12776180
J Biol Chem. 2004 Mar 5;279(10):8867-72
14684748
Mol Biol Cell. 2008 Dec;19(12):5279-88
18829863
Cell Stress Chaperones. 1996 Apr;1(1):23-8
9222585
Mol Biol Cell. 1996 Sep;7(9):1455-69
8885239
Biochem Biophys Res Commun. 1999 Dec 9;266(1):147-51
10581180
J Biol Chem. 1995 Oct 20;270(42):24818-25
7559602
Int J Cancer. 2004 Feb 20;108(5):704-11
14696097
Nat Struct Mol Biol. 2005 Jun;12(6):497-504
15908962
EMBO J. 2006 Jun 7;25(11):2510-8
16688211
J Biol Chem. 1994 Apr 29;269(17):12893-8
8175706
Mol Biol Cell. 2001 Dec;12(12):3773-82
11739779
J Biol Chem. 1996 Jul 5;271(27):15874-8
8663302
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4209-14
11929994
Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10064-9
16002468
Genes Cells. 2000 Sep;5(9):699-709
10971652
Nat Struct Mol Biol. 2009 Jun;16(6):589-97
19491936
J Mol Biol. 1996 Nov 15;263(5):657-70
8947566
Nat Struct Mol Biol. 2009 Jun;16(6):574-81
19491934
Int J Cancer. 2003 Aug 20;106(2):224-31
12800198
Nat Rev Mol Cell Biol. 2004 Feb;5(2):158-63
15040448
Biochemistry. 2000 Jun 20;39(24):7236-44
10852723
EMBO J. 1998 Aug 17;17(16):4809-17
9707440
Anal Biochem. 1987 Nov 1;166(2):368-79
2449095
Nature. 2010 Dec 23;468(7327):1124-8
21179169
EMBO J. 1999 Jan 4;18(1):85-95
9878053
Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1558-63
17242366
J Biol Chem. 2007 Mar 16;282(11):7809-16
17229726
BMC Evol Biol. 2008 Jan 23;8:19
18215318
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1948-52
1705713
Cell Stress Chaperones. 2009 Jan;14(1):1-21
18686016
Biochem Pharmacol. 1977 Apr 15;26(8):705-10
856202