• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Dec 1996; 16(12): 6623–6633.
PMCID: PMC231664

Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors.

Abstract

Understanding how cyclin-cdk complexes recognize their substrates is a central problem in cell cycle biology. We identified an E2F1-derived eight-residue peptide which blocked the binding of cyclin A and E-cdk2 complexes to E2F1 and p21. Short peptides spanning similar sequences in p107, p130, and p21-like cdk inhibitors likewise bound to cyclin A-cdk2 and cyclin E-cdk2. In addition, these peptides promoted formation of stable cyclin A-cdk2 complexes in vitro but inhibited the phosphorylation of the retinoblastoma protein by cyclin A- but not cyclin B-associated kinases. Mutation of the cyclin-cdk2 binding motifs in p107 and E2F1 likewise prevented their phosphorylation by cyclin A-associated kinases in vitro. The cdk inhibitor p21 was found to contain two functional copies of this recognition motif, as determined by in vitro kinase binding/inhibition assays and in vivo growth suppression assays. Thus, these studies have identified a cyclin A- and E-cdk2 substrate recognition motif. Furthermore, these data suggest that p21-like cdk inhibitors function, at least in part, by blocking the interaction of substrates with cyclin-cdk2 complexes.

Full Text

The Full Text of this article is available as a PDF (743K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ando K, Ajchenbaum-Cymbalista F, Griffin JD. Regulation of G1/S transition by cyclins D2 and D3 in hematopoietic cells. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9571–9575. [PMC free article] [PubMed]
  • Baldin V, Lukas J, Marcote MJ, Pagano M, Draetta G. Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev. 1993 May;7(5):812–821. [PubMed]
  • Bartkova J, Lukas J, Müller H, Lützhøft D, Strauss M, Bartek J. Cyclin D1 protein expression and function in human breast cancer. Int J Cancer. 1994 May 1;57(3):353–361. [PubMed]
  • Beijersbergen RL, Hijmans EM, Zhu L, Bernards R. Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation. EMBO J. 1994 Sep 1;13(17):4080–4086. [PMC free article] [PubMed]
  • Chen C, Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. [PMC free article] [PubMed]
  • Chen IT, Akamatsu M, Smith ML, Lung FD, Duba D, Roller PP, Fornace AJ, Jr, O'Connor PM. Characterization of p21Cip1/Waf1 peptide domains required for cyclin E/Cdk2 and PCNA interaction. Oncogene. 1996 Feb 1;12(3):595–607. [PubMed]
  • Chen J, Jackson PK, Kirschner MW, Dutta A. Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. Nature. 1995 Mar 23;374(6520):386–388. [PubMed]
  • Cobrinik D, Whyte P, Peeper DS, Jacks T, Weinberg RA. Cell cycle-specific association of E2F with the p130 E1A-binding protein. Genes Dev. 1993 Dec;7(12A):2392–2404. [PubMed]
  • Dimri GP, Nakanishi M, Desprez PY, Smith JR, Campisi J. Inhibition of E2F activity by the cyclin-dependent protein kinase inhibitor p21 in cells expressing or lacking a functional retinoblastoma protein. Mol Cell Biol. 1996 Jun;16(6):2987–2997. [PMC free article] [PubMed]
  • Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, Weinberg RA. Physical interaction of the retinoblastoma protein with human D cyclins. Cell. 1993 May 7;73(3):499–511. [PubMed]
  • Dynlacht BD, Flores O, Lees JA, Harlow E. Differential regulation of E2F transactivation by cyclin/cdk2 complexes. Genes Dev. 1994 Aug 1;8(15):1772–1786. [PubMed]
  • Ewen ME, Faha B, Harlow E, Livingston DM. Interaction of p107 with cyclin A independent of complex formation with viral oncoproteins. Science. 1992 Jan 3;255(5040):85–87. [PubMed]
  • Ewen ME, Sluss HK, Sherr CJ, Matsushime H, Kato J, Livingston DM. Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. Cell. 1993 May 7;73(3):487–497. [PubMed]
  • Ewen ME, Xing YG, Lawrence JB, Livingston DM. Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Cell. 1991 Sep 20;66(6):1155–1164. [PubMed]
  • Fagan R, Flint KJ, Jones N. Phosphorylation of E2F-1 modulates its interaction with the retinoblastoma gene product and the adenoviral E4 19 kDa protein. Cell. 1994 Sep 9;78(5):799–811. [PubMed]
  • Faha B, Ewen ME, Tsai LH, Livingston DM, Harlow E. Interaction between human cyclin A and adenovirus E1A-associated p107 protein. Science. 1992 Jan 3;255(5040):87–90. [PubMed]
  • Fotedar R, Fitzgerald P, Rousselle T, Cannella D, Dorée M, Messier H, Fotedar A. p21 contains independent binding sites for cyclin and cdk2: both sites are required to inhibit cdk2 kinase activity. Oncogene. 1996 May 16;12(10):2155–2164. [PubMed]
  • Frangioni JV, Neel BG. Solubilization and purification of enzymatically active glutathione S-transferase (pGEX) fusion proteins. Anal Biochem. 1993 Apr;210(1):179–187. [PubMed]
  • Girard F, Strausfeld U, Fernandez A, Lamb NJ. Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Cell. 1991 Dec 20;67(6):1169–1179. [PubMed]
  • Goubin F, Ducommun B. Identification of binding domains on the p21Cip1 cyclin-dependent kinase inhibitor. Oncogene. 1995 Jun 15;10(12):2281–2287. [PubMed]
  • Gu W, Bhatia K, Magrath IT, Dang CV, Dalla-Favera R. Binding and suppression of the Myc transcriptional activation domain by p107. Science. 1994 Apr 8;264(5156):251–254. [PubMed]
  • Gu Y, Turck CW, Morgan DO. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature. 1993 Dec 16;366(6456):707–710. [PubMed]
  • Hall FL, Williams RT, Wu L, Wu F, Carbonaro-Hall DA, Harper JW, Warburton D. Two potentially oncogenic cyclins, cyclin A and cyclin D1, share common properties of subunit configuration, tyrosine phosphorylation and physical association with the Rb protein. Oncogene. 1993 May;8(5):1377–1384. [PubMed]
  • Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805–816. [PubMed]
  • Hiebert SW. Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression. Mol Cell Biol. 1993 Jun;13(6):3384–3391. [PMC free article] [PubMed]
  • Hiebert SW, Chellappan SP, Horowitz JM, Nevins JR. The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dev. 1992 Feb;6(2):177–185. [PubMed]
  • Hinds PW, Mittnacht S, Dulic V, Arnold A, Reed SI, Weinberg RA. Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell. 1992 Sep 18;70(6):993–1006. [PubMed]
  • Hoang AT, Lutterbach B, Lewis BC, Yano T, Chou TY, Barrett JF, Raffeld M, Hann SR, Dang CV. A link between increased transforming activity of lymphoma-derived MYC mutant alleles, their defective regulation by p107, and altered phosphorylation of the c-Myc transactivation domain. Mol Cell Biol. 1995 Aug;15(8):4031–4042. [PMC free article] [PubMed]
  • Hunter T, Pines J. Cyclins and cancer. Cell. 1991 Sep 20;66(6):1071–1074. [PubMed]
  • Hunter T, Pines J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994 Nov 18;79(4):573–582. [PubMed]
  • Kaelin WG, Jr, Krek W, Sellers WR, DeCaprio JA, Ajchenbaum F, Fuchs CS, Chittenden T, Li Y, Farnham PJ, Blanar MA, et al. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell. 1992 Jul 24;70(2):351–364. [PubMed]
  • Kaelin WG, Jr, Pallas DC, DeCaprio JA, Kaye FJ, Livingston DM. Identification of cellular proteins that can interact specifically with the T/E1A-binding region of the retinoblastoma gene product. Cell. 1991 Feb 8;64(3):521–532. [PubMed]
  • Kato JY, Sherr CJ. Inhibition of granulocyte differentiation by G1 cyclins D2 and D3 but not D1. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11513–11517. [PMC free article] [PubMed]
  • Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993 Mar;7(3):331–342. [PubMed]
  • Koh J, Enders GH, Dynlacht BD, Harlow E. Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition. Nature. 1995 Jun 8;375(6531):506–510. [PubMed]
  • Nilsen TW. RNA-RNA interactions in the spliceosome: unraveling the ties that bind. Cell. 1994 Jul 15;78(1):1–4. [PubMed]
  • Lees E. Cyclin dependent kinase regulation. Curr Opin Cell Biol. 1995 Dec;7(6):773–780. [PubMed]
  • Lees E, Faha B, Dulic V, Reed SI, Harlow E. Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner. Genes Dev. 1992 Oct;6(10):1874–1885. [PubMed]
  • Lees JA, Buchkovich KJ, Marshak DR, Anderson CW, Harlow E. The retinoblastoma protein is phosphorylated on multiple sites by human cdc2. EMBO J. 1991 Dec;10(13):4279–4290. [PMC free article] [PubMed]
  • Li Y, Graham C, Lacy S, Duncan AM, Whyte P. The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E. Genes Dev. 1993 Dec;7(12A):2366–2377. [PubMed]
  • Lin BT, Gruenwald S, Morla AO, Lee WH, Wang JY. Retinoblastoma cancer suppressor gene product is a substrate of the cell cycle regulator cdc2 kinase. EMBO J. 1991 Apr;10(4):857–864. [PMC free article] [PubMed]
  • Lin J, Reichner C, Wu X, Levine AJ. Analysis of wild-type and mutant p21WAF-1 gene activities. Mol Cell Biol. 1996 Apr;16(4):1786–1793. [PMC free article] [PubMed]
  • Lukas J, Bartkova J, Rohde M, Strauss M, Bartek J. Cyclin D1 is dispensable for G1 control in retinoblastoma gene-deficient cells independently of cdk4 activity. Mol Cell Biol. 1995 May;15(5):2600–2611. [PMC free article] [PubMed]
  • Lukas J, Müller H, Bartkova J, Spitkovsky D, Kjerulff AA, Jansen-Dürr P, Strauss M, Bartek J. DNA tumor virus oncoproteins and retinoblastoma gene mutations share the ability to relieve the cell's requirement for cyclin D1 function in G1. J Cell Biol. 1994 May;125(3):625–638. [PMC free article] [PubMed]
  • Lukas J, Parry D, Aagaard L, Mann DJ, Bartkova J, Strauss M, Peters G, Bartek J. Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. Nature. 1995 Jun 8;375(6531):503–506. [PubMed]
  • Luo Y, Hurwitz J, Massagué J. Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cip1. Nature. 1995 May 11;375(6527):159–161. [PubMed]
  • Marsilio E, Cheng SH, Schaffhausen B, Paucha E, Livingston DM. The T/t common region of simian virus 40 large T antigen contains a distinct transformation-governing sequence. J Virol. 1991 Oct;65(10):5647–5652. [PMC free article] [PubMed]
  • Matsushime H, Quelle DE, Shurtleff SA, Shibuya M, Sherr CJ, Kato JY. D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol. 1994 Mar;14(3):2066–2076. [PMC free article] [PubMed]
  • Meyerson M, Harlow E. Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Mol Cell Biol. 1994 Mar;14(3):2077–2086. [PMC free article] [PubMed]
  • Morgan DO. Principles of CDK regulation. Nature. 1995 Mar 9;374(6518):131–134. [PubMed]
  • Müller H, Lukas J, Schneider A, Warthoe P, Bartek J, Eilers M, Strauss M. Cyclin D1 expression is regulated by the retinoblastoma protein. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2945–2949. [PMC free article] [PubMed]
  • Musgrove EA, Lee CS, Buckley MF, Sutherland RL. Cyclin D1 induction in breast cancer cells shortens G1 and is sufficient for cells arrested in G1 to complete the cell cycle. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8022–8026. [PMC free article] [PubMed]
  • Nakanishi M, Robetorye RS, Adami GR, Pereira-Smith OM, Smith JR. Identification of the active region of the DNA synthesis inhibitory gene p21Sdi1/CIP1/WAF1. EMBO J. 1995 Feb 1;14(3):555–563. [PMC free article] [PubMed]
  • Nigg EA. The substrates of the cdc2 kinase. Semin Cell Biol. 1991 Aug;2(4):261–270. [PubMed]
  • Norbury C, Nurse P. Animal cell cycles and their control. Annu Rev Biochem. 1992;61:441–470. [PubMed]
  • Ohtsubo M, Roberts JM. Cyclin-dependent regulation of G1 in mammalian fibroblasts. Science. 1993 Mar 26;259(5103):1908–1912. [PubMed]
  • Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM, Pagano M. Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol Cell Biol. 1995 May;15(5):2612–2624. [PMC free article] [PubMed]
  • Pagano M, Pepperkok R, Verde F, Ansorge W, Draetta G. Cyclin A is required at two points in the human cell cycle. EMBO J. 1992 Mar;11(3):961–971. [PMC free article] [PubMed]
  • Peeper DS, Keblusek P, Helin K, Toebes M, van der Eb AJ, Zantema A. Phosphorylation of a specific cdk site in E2F-1 affects its electrophoretic mobility and promotes pRB-binding in vitro. Oncogene. 1995 Jan 5;10(1):39–48. [PubMed]
  • Peeper DS, Parker LL, Ewen ME, Toebes M, Hall FL, Xu M, Zantema A, van der Eb AJ, Piwnica-Worms H. A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. EMBO J. 1993 May;12(5):1947–1954. [PMC free article] [PubMed]
  • Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, Massagué J. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell. 1994 Jul 15;78(1):59–66. [PubMed]
  • Qin XQ, Chittenden T, Livingston DM, Kaelin WG., Jr Identification of a growth suppression domain within the retinoblastoma gene product. Genes Dev. 1992 Jun;6(6):953–964. [PubMed]
  • Qin XQ, Livingston DM, Ewen M, Sellers WR, Arany Z, Kaelin WG., Jr The transcription factor E2F-1 is a downstream target of RB action. Mol Cell Biol. 1995 Feb;15(2):742–755. [PMC free article] [PubMed]
  • Quelle DE, Ashmun RA, Shurtleff SA, Kato JY, Bar-Sagi D, Roussel MF, Sherr CJ. Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev. 1993 Aug;7(8):1559–1571. [PubMed]
  • Resnitzky D, Gossen M, Bujard H, Reed SI. Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system. Mol Cell Biol. 1994 Mar;14(3):1669–1679. [PMC free article] [PubMed]
  • Resnitzky D, Hengst L, Reed SI. Cyclin A-associated kinase activity is rate limiting for entrance into S phase and is negatively regulated in G1 by p27Kip1. Mol Cell Biol. 1995 Aug;15(8):4347–4352. [PMC free article] [PubMed]
  • Resnitzky D, Reed SI. Different roles for cyclins D1 and E in regulation of the G1-to-S transition. Mol Cell Biol. 1995 Jul;15(7):3463–3469. [PMC free article] [PubMed]
  • Rosenberg AR, Zindy F, Le Deist F, Mouly H, Métézeau P, Bréchot C, Lamas E. Overexpression of human cyclin A advances entry into S phase. Oncogene. 1995 Apr 20;10(8):1501–1509. [PubMed]
  • Russo AA, Jeffrey PD, Patten AK, Massagué J, Pavletich NP. Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature. 1996 Jul 25;382(6589):325–331. [PubMed]
  • Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995 May 15;9(10):1149–1163. [PubMed]
  • Shirodkar S, Ewen M, DeCaprio JA, Morgan J, Livingston DM, Chittenden T. The transcription factor E2F interacts with the retinoblastoma product and a p107-cyclin A complex in a cell cycle-regulated manner. Cell. 1992 Jan 10;68(1):157–166. [PubMed]
  • Shiyanov P, Bagchi S, Adami G, Kokontis J, Hay N, Arroyo M, Morozov A, Raychaudhuri P. p21 Disrupts the interaction between cdk2 and the E2F-p130 complex. Mol Cell Biol. 1996 Mar;16(3):737–744. [PMC free article] [PubMed]
  • Smith EJ, Nevins JR. The Rb-related p107 protein can suppress E2F function independently of binding to cyclin A/cdk2. Mol Cell Biol. 1995 Jan;15(1):338–344. [PMC free article] [PubMed]
  • Songyang Z, Blechner S, Hoagland N, Hoekstra MF, Piwnica-Worms H, Cantley LC. Use of an oriented peptide library to determine the optimal substrates of protein kinases. Curr Biol. 1994 Nov 1;4(11):973–982. [PubMed]
  • Srinivasan J, Koszelak M, Mendelow M, Kwon YG, Lawrence DS. The design of peptide-based substrates for the cdc2 protein kinase. Biochem J. 1995 Aug 1;309(Pt 3):927–931. [PMC free article] [PubMed]
  • Su JY, Rempel RE, Erikson E, Maller JL. Cloning and characterization of the Xenopus cyclin-dependent kinase inhibitor p27XIC1. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10187–10191. [PMC free article] [PubMed]
  • Toyoshima H, Hunter T. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell. 1994 Jul 15;78(1):67–74. [PubMed]
  • Vairo G, Livingston DM, Ginsberg D. Functional interaction between E2F-4 and p130: evidence for distinct mechanisms underlying growth suppression by different retinoblastoma protein family members. Genes Dev. 1995 Apr 1;9(7):869–881. [PubMed]
  • van den Heuvel S, Harlow E. Distinct roles for cyclin-dependent kinases in cell cycle control. Science. 1993 Dec 24;262(5142):2050–2054. [PubMed]
  • Warbrick E, Lane DP, Glover DM, Cox LS. A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. Curr Biol. 1995 Mar 1;5(3):275–282. [PubMed]
  • Williams RT, Carbonaro-Hall DA, Hall FL. Co-purification of p34cdc2/p58cyclin A proline-directed protein kinase and the retinoblastoma tumor susceptibility gene product: interaction of an oncogenic serine/threonine protein kinase with a tumor-suppressor protein. Oncogene. 1992 Mar;7(3):423–432. [PubMed]
  • Wilson IA, Haft DH, Getzoff ED, Tainer JA, Lerner RA, Brenner S. Identical short peptide sequences in unrelated proteins can have different conformations: a testing ground for theories of immune recognition. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5255–5259. [PMC free article] [PubMed]
  • Wimmel A, Lucibello FC, Sewing A, Adolph S, Müller R. Inducible acceleration of G1 progression through tetracycline-regulated expression of human cyclin E. Oncogene. 1994 Mar;9(3):995–997. [PubMed]
  • Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993 Dec 16;366(6456):701–704. [PubMed]
  • Xiong Y, Zhang H, Beach D. Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes Dev. 1993 Aug;7(8):1572–1583. [PubMed]
  • Xu M, Sheppard KA, Peng CY, Yee AS, Piwnica-Worms H. Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation. Mol Cell Biol. 1994 Dec;14(12):8420–8431. [PMC free article] [PubMed]
  • Zhang H, Hannon GJ, Beach D. p21-containing cyclin kinases exist in both active and inactive states. Genes Dev. 1994 Aug 1;8(15):1750–1758. [PubMed]
  • Zhang J, Sanchez RJ, Wang S, Guarnaccia C, Tossi A, Zahariev S, Pongor S. Substrate specificity of CDC2 kinase from human HeLa cells as determined with synthetic peptides and molecular modeling. Arch Biochem Biophys. 1994 Dec;315(2):415–424. [PubMed]
  • Zhu L, Enders G, Lees JA, Beijersbergen RL, Bernards R, Harlow E. The pRB-related protein p107 contains two growth suppression domains: independent interactions with E2F and cyclin/cdk complexes. EMBO J. 1995 May 1;14(9):1904–1913. [PMC free article] [PubMed]
  • Zhu L, Harlow E, Dynlacht BD. p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F. Genes Dev. 1995 Jul 15;9(14):1740–1752. [PubMed]
  • Zhu L, van den Heuvel S, Helin K, Fattaey A, Ewen M, Livingston D, Dyson N, Harlow E. Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. Genes Dev. 1993 Jul;7(7A):1111–1125. [PubMed]
  • Zindy F, Lamas E, Chenivesse X, Sobczak J, Wang J, Fesquet D, Henglein B, Bréchot C. Cyclin A is required in S phase in normal epithelial cells. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1144–1154. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...