Home LiteratureArticle Details
PMID: 2009861 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Retinoblastoma cancer suppressor gene product is a substrate of the cell cycle regulator cdc2 kinase.

The EMBO journal ·Vol. 10 ·No. 4 ·1991-04-00 ·Pages 857-64

Lin BT, Gruenwald S, Morla AO, Lee WH, Wang JY

Abstract

The retinoblastoma gene product (RB) is a nuclear protein which has been shown to function as a tumor suppressor. It is phosphorylated from S to M phase of the cell cycle and dephosphorylated in G1. This suggests that the function of RB is regulated by its phosphorylation in the cell cycle. Ten phosphotryptic peptides are found in human RB proteins. The pattern of RB phosphorylation does not change from S to M phases of the cell cycle. Hypophosphorylated RB prepared from insect cells infected with an RB-recombinant baculovirus is used as a substrate for in vitro phosphorylation reactions. Of several protein kinases tested, only cdc2 kinase phosphorylates RB efficiently and all 10 peptides can be phosphorylated by cdc2 in vitro. Removal of cdc2 from mitotic cell extracts by immunoprecipitation causes a concomitant depletion of RB kinase activity. These results indicate that cdc2 or a kinase with similar substrate specificity is involved in the cell cycle-dependent phosphorylation of the RB protein.

MeSH Terms
CDC2 Protein Kinase/metabolism Cell Cycle Cell Line Genes, Retinoblastoma HeLa Cells/cytology,metabolism Humans Mitosis Nuclear Proteins/genetics,metabolism Peptide Mapping Phosphopeptides/isolation & purification Phosphorylation Retinoblastoma Protein/genetics,metabolism
Chemicals
Nuclear Proteins Phosphopeptides Retinoblastoma Protein CDC2 Protein Kinase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lin B T
Department of Biology, University of California, San Diego, La Jolla 92093-0116.
Gruenwald S
Morla A O
Lee W H
Wang J Y
References (47)
47 references, click to expand
  1. Genetic control of the cell division cycle in the fission yeast Schizosaccharomyces pombe.
    Mol Gen Genet. 1976 Jul 23;146(2):167-78 PMID: 958201
  2. Mutation and cancer: statistical study of retinoblastoma.
    Proc Natl Acad Sci U S A. 1971 Apr;68(4):820-3 PMID: 5279523
  3. Genetics of retinoblastoma.
    Hum Genet. 1979 Nov 1;52(1):1-54 PMID: 393614
  4. Production of large numbers of mitotic mammalian cells by use of the reversible microtubule inhibitor nocodazole. Nocodazole accumulated mitotic cells.
    Exp Cell Res. 1980 Apr;126(2):397-405 PMID: 6153987
  5. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine.
    Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311-5 PMID: 6246487
  6. Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast.
    Nature. 1981 Aug 6;292(5823):558-60 PMID: 7254352
  7. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma.
    Nature. 1983 Oct 27-Nov 2;305(5937):779-84 PMID: 6633649
  8. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma.
    Nature. 1986 Oct 16-22;323(6089):643-6 PMID: 2877398
  9. Human retinoblastoma susceptibility gene: cloning, identification, and sequence.
    Science. 1987 Mar 13;235(4794):1394-9 PMID: 3823889
  10. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2.
    Nature. 1987 May 7-13;327(6117):31-5 PMID: 3553962
  11. Identification of p34 and p13, human homologs of the cell cycle regulators of fission yeast encoded by cdc2+ and suc1+.
    Cell. 1987 Jul 17;50(2):319-25 PMID: 3297353
  12. Structural evidence for the authenticity of the human retinoblastoma gene.
    Science. 1987 Jun 26;236(4809):1657-61 PMID: 2885916
  13. The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity.
    Nature. 1987 Oct 15-21;329(6140):642-5 PMID: 3657987
  14. Purification of maturation-promoting factor, an intracellular regulator of early mitotic events.
    Proc Natl Acad Sci U S A. 1988 May;85(9):3009-13 PMID: 3283736
  15. Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement.
    Cell. 1988 Jul 1;54(1):17-26 PMID: 3289755
  16. The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis.
    Cell. 1988 Jul 29;54(3):423-31 PMID: 3293802
  17. Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+.
    Cell. 1988 Jul 29;54(3):433-9 PMID: 3293803
  18. cdc2 is a component of the M phase-specific histone H1 kinase: evidence for identity with MPF.
    Cell. 1988 Oct 21;55(2):371-8 PMID: 2844417
  19. Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells.
    Science. 1988 Dec 16;242(4885):1563-6 PMID: 3201247
  20. High level expression of nonfused foreign genes with Autographa californica nuclear polyhedrosis virus expression vectors.
    Virology. 1989 May;170(1):31-9 PMID: 2497580
  21. Purified maturation promoting factor phosphorylates pp60c-src at the sites phosphorylated during fibroblast mitosis.
    Cell. 1989 Jun 2;57(5):763-74 PMID: 2470512
  22. Mitosis-specific phosphorylation of p60c-src by p34cdc2-associated protein kinase.
    Cell. 1989 Jun 2;57(5):775-86 PMID: 2470513
  23. Human retinoblastoma gene: long-range mapping and analysis of its deletion in a breast cancer cell line.
    Mol Cell Biol. 1989 Apr;9(4):1628-34 PMID: 2725521
  24. Dephosphorylation and activation of Xenopus p34cdc2 protein kinase during the cell cycle.
    Nature. 1989 Jun 22;339(6226):626-9 PMID: 2543932
  25. Antibodies detecting abnormalities of the retinoblastoma susceptibility gene product (pp110RB) in osteosarcomas and synovial sarcomas.
    Oncogene Res. 1989;4(3):205-14 PMID: 2740144
  26. Reversible tyrosine phosphorylation of cdc2: dephosphorylation accompanies activation during entry into mitosis.
    Cell. 1989 Jul 14;58(1):193-203 PMID: 2473839
  27. Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2.
    Cell. 1989 Sep 8;58(5):833-46 PMID: 2570636
  28. A 60 kd cdc2-associated polypeptide complexes with the E1A proteins in adenovirus-infected cells.
    Cell. 1989 Sep 8;58(5):981-90 PMID: 2570639
  29. The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element.
    Cell. 1989 Sep 22;58(6):1085-95 PMID: 2673542
  30. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle.
    Cell. 1989 Sep 22;58(6):1097-105 PMID: 2673543
  31. Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation.
    Cell. 1989 Sep 22;58(6):1193-8 PMID: 2673546
  32. Identification of a novel proline-directed serine/threonine protein kinase in rat pheochromocytoma.
    J Biol Chem. 1989 Sep 25;264(27):16292-8 PMID: 2570779
  33. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis.
    Nature. 1989 Nov 2;342(6245):39-45 PMID: 2682257
  34. Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product.
    Science. 1989 Dec 8;246(4935):1300-3 PMID: 2588006
  35. Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene.
    Science. 1990 Feb 9;247(4943):712-5 PMID: 2300823
  36. The retinoblastoma susceptibility gene product undergoes cell cycle-dependent dephosphorylation and binding to and release from SV40 large T.
    Cell. 1990 Feb 9;60(3):387-96 PMID: 2154332
  37. Universal control mechanism regulating onset of M-phase.
    Nature. 1990 Apr 5;344(6266):503-8 PMID: 2138713
  38. Expression and state of phosphorylation of the retinoblastoma susceptibility gene product in cycling and noncycling human hematopoietic cells.
    Proc Natl Acad Sci U S A. 1990 Apr;87(7):2770-4 PMID: 2320588
  39. Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells.
    Proc Natl Acad Sci U S A. 1990 Apr;87(7):2775-9 PMID: 2181449
  40. Differential phosphorylation of c-Abl in cell cycle determined by cdc2 kinase and phosphatase activity.
    Science. 1990 Apr 13;248(4952):217-20 PMID: 2183353
  41. In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase.
    Cell. 1990 May 18;61(4):591-602 PMID: 2188731
  42. Transfer of proteins to membranes facilitates both cyanogen bromide cleavage and two-dimensional proteolytic mapping.
    Oncogene. 1990 Jun;5(6):921-3 PMID: 1688326
  43. cAMP-dependent protein kinase: framework for a diverse family of regulatory enzymes.
    Annu Rev Biochem. 1990;59:971-1005 PMID: 2165385
  44. Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B.
    Nature. 1990 Aug 23;346(6286):760-3 PMID: 2143810
  45. A cdc2-like protein is involved in the initiation of DNA replication in Xenopus egg extracts.
    Cell. 1990 Sep 7;62(5):855-62 PMID: 2203536
  46. Cell cycle control of DNA replication by a homologue from human cells of the p34cdc2 protein kinase.
    Science. 1990 Nov 9;250(4982):786-91 PMID: 2173140
  47. Retinoblastoma and subband deletion of chromosome 13.
    Am J Dis Child. 1978 Feb;132(2):161-3 PMID: 626181
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-04-00
Pages
857-64
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452726
Subset
IM
Grants
NCI NIH HHS · R01 CA058320 · United States
NCI NIH HHS · CA 43045 · United States
NCI NIH HHS · CA 51495 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com