|
|
 Previous Article | Table of Contents | Next Article 
The Fanconi Anemia Polypeptide, FAC, Binds to the Cyclin-Dependent Kinase, cdc2
Gary M. Kupfer,
Takayuki Yamashita,
Dieter Naf,
Ahmed Suliman,
Shigetaka Asano, and
Alan D. D'Andrea
From the Division of Pediatric Oncology and Cellular and Molecular Biology, Dana-Farber Cancer Institute Boston, MA; the Department of Hematology, Children's Hospital, Harvard Medical School, Boston, MA; and The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Fanconi anemia (FA) is an autosomal recessive disorder characterized by developmental defects, bone marrow failure, and cancer susceptibility. Cells derived from FA patients are sensitive to crosslinking agents and have a prolonged G2 phase, suggesting a cell cycle abnormality. Although transfection of type-C FA cells with the FAC cDNA corrects these cellular abnormalities, the molecular function of the FAC polypeptide remains unknown. In the current study we show that expression of the FAC polypeptide is regulated during cell cycle progression. In synchronized HeLa cells, FAC protein expression increased during S phase, was maximal at the G2 /M transition, and declined during M phase. In addition, the FAC protein coimmunoprecipitated with the cyclin-dependent kinase, cdc2. We next tested various mutant forms of the FAC polypeptide for binding to cdc2. A patient-derived mutant FAC polypeptide, containing a point mutation at L554P, failed to bind to cdc2. The FAC/cdc2 binding interaction therefore correlated with the functional activity of the FAC protein. Moreover, binding of FAC to cdc2 was mediated by the carboxyl-terminal 50 amino acids of FAC in a region of the protein required for FAC function. Taken together, our results suggest that the binding of FAC and cdc2 is required for normal G2 /M progression in mammalian cells. Absence of a functional interaction between FAC and cdc2 in FA cells may underlie the cell cycle abnormality and clinical abnormalities of FA.
Blood, Vol. 90 No. 3 (August 1), 1997:
pp. 1047-1054
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Montes de Oca, P. R. Andreassen, S. P. Margossian, R. C. Gregory, T. Taniguchi, X. Wang, S. Houghtaling, M. Grompe, and A. D. D'Andrea
Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin
Blood,
February 1, 2005;
105(3):
1003 - 1009.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. W. Freie, S. L. M. Ciccone, X. Li, P. A. Plett, C. M. Orschell, E. F. Srour, H. Hanenberg, D. Schindler, S.-H. Lee, and D. W. Clapp
A Role for the Fanconi Anemia C Protein in Maintaining the DNA Damage-induced G2 Checkpoint
J. Biol. Chem.,
December 3, 2004;
279(49):
50986 - 50993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mi, F. Qiao, J. B. Wilson, A. A. High, M. J. Schroeder, P. T. Stukenberg, A. Moss, J. Shabanowitz, D. F. Hunt, N. J. Jones, et al.
FANCG Is Phosphorylated at Serines 383 and 387 during Mitosis
Mol. Cell. Biol.,
October 1, 2004;
24(19):
8576 - 8585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Thomashevski, A. A. High, M. Drozd, J. Shabanowitz, D. F. Hunt, P. A. Grant, and G. M. Kupfer
The Fanconi Anemia Core Complex Forms Four Complexes of Different Sizes in Different Subcellular Compartments
J. Biol. Chem.,
June 18, 2004;
279(25):
26201 - 26209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Lamerdin, N. A. Yamada, J. W. George, B. Souza, A. T. Christian, N. J. Jones, and L. H. Thompson
Characterization of the hamster FancG/Xrcc9 gene and mutations in CHO UV40 and NM3
Mutagenesis,
May 1, 2004;
19(3):
237 - 244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Brodeur, I. Goulet, C. S. Tremblay, C. Charbonneau, M.-C. Delisle, C. Godin, C. Huard, E. W. Khandjian, M. Buchwald, G. Levesque, et al.
Regulation of the Fanconi Anemia Group C Protein through Proteolytic Modification
J. Biol. Chem.,
February 6, 2004;
279(6):
4713 - 4720.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M D Tischkowitz and S V Hodgson
Fanconi anaemia
J. Med. Genet.,
January 1, 2003;
40(1):
1 - 10.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Bogliolo, O. Cabre, E. Callen, V. Castillo, A. Creus, R. Marcos, and J. Surralles
The Fanconi anaemia genome stability and tumour suppressor network
Mutagenesis,
November 1, 2002;
17(6):
529 - 538.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Taniguchi, I. Garcia-Higuera, P. R. Andreassen, R. C. Gregory, M. Grompe, and A. D. D'Andrea
S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51
Blood,
September 18, 2002;
100(7):
2414 - 2420.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yagasaki, D. Adachi, T. Oda, I. Garcia-Higuera, N. Tetteh, A. D. D'Andrea, M. Futaki, S. Asano, and T. Yamashita
A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA
Blood,
December 15, 2001;
98(13):
3650 - 3657.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Grompe and A. D'Andrea
Fanconi anemia and DNA repair
Hum. Mol. Genet.,
October 1, 2001;
10(20):
2253 - 2259.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Pang, T. A. Christianson, W. Keeble, J. Diaz, G. R. Faulkner, C. Reifsteck, S. Olson, and G. C. Bagby
The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality
Blood,
September 1, 2001;
98(5):
1392 - 1401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Heinrich, K. V. Silvey, S. Stone, A. J. Zigler, D. J. Griffith, M. Montalto, L. Chai, Y. Zhi, and M. E. Hoatlin
Posttranscriptional cell cycle-dependent regulation of human FANCC expression
Blood,
June 15, 2000;
95(12):
3970 - 3977.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. G. Korkina, I. B. Deeva, A. De Biase, M. Iaccarino, R. Oral, M. Warnau, and G. Pagano
Redox-dependent toxicity of diepoxybutane and mitomycin C in sea urchin embryogenesis
Carcinogenesis,
February 1, 2000;
21(2):
213 - 220.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Hoatlin, Y. Zhi, H. Ball, K. Silvey, A. Melnick, S. Stone, S. Arai, N. Hawe, G. Owen, A. Zelent, et al.
A Novel BTB/POZ Transcriptional Repressor Protein Interacts With the Fanconi Anemia Group C Protein and PLZF
Blood,
December 1, 1999;
94(11):
3737 - 3747.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Garcia-Higuera, Y. Kuang, D. Naf, J. Wasik, and A. D. D'Andrea
Fanconi Anemia Proteins FANCA, FANCC, and FANCG/XRCC9 Interact in a Functional Nuclear Complex
Mol. Cell. Biol.,
July 1, 1999;
19(7):
4866 - 4873.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. S. Haneline, T. A. Gobbett, R. Ramani, M. Carreau, M. Buchwald, M. C. Yoder, and D. W. Clapp
Loss of FancC Function Results in Decreased Hematopoietic Stem Cell Repopulating Ability
Blood,
July 1, 1999;
94(1):
1 - 8.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A.E. Kruyt, T. Hoshino, J. M. Liu, P. Joseph, A. K. Jaiswal, and H. Youssoufian
Abnormal Microsomal Detoxification Implicated in Fanconi Anemia Group C by Interaction of the FAC Protein With NADPH Cytochrome P450 Reductase
Blood,
November 1, 1998;
92(9):
3050 - 3056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yamashita, G. M. Kupfer, D. Naf, A. Suliman, H. Joenje, S. Asano, and A. D. D'Andrea
The Fanconi anemia pathway requires FAA phosphorylation and FAA/FAC nuclear accumulation
PNAS,
October 27, 1998;
95(22):
13085 - 13090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Näf, G. M. Kupfer, A. Suliman, K. Lambert, and A. D. D'Andrea
Functional Activity of the Fanconi Anemia Protein FAA Requires FAC Binding and Nuclear Localization
Mol. Cell. Biol.,
October 1, 1998;
18(10):
5952 - 5960.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
F. A.E. Kruyt and H. Youssoufian
The Fanconi Anemia Proteins FAA and FAC Function in Different Cellular Compartments to Protect Against Cross-Linking Agent Cytotoxicity
Blood,
October 1, 1998;
92(7):
2229 - 2236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hoshino, J. Wang, M. P. Devetten, N. Iwata, S. Kajigaya, R. J. Wise, J. M. Liu, and H. Youssoufian
Molecular Chaperone GRP94 Binds to the Fanconi Anemia Group C Protein and Regulates Its Intracellular Expression
Blood,
June 1, 1998;
91(11):
4379 - 4386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Hoatlin, T. A. Christianson, W. W. Keeble, A. T. Hammond, Y. Zhi, M. C. Heinrich, P. A. Tower, and G. C. Bagby Jr
The Fanconi Anemia Group C Gene Product Is Located in Both the Nucleus and Cytoplasm of Human Cells
Blood,
February 15, 1998;
91(4):
1418 - 1425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Heinrich, M. E. Hoatlin, A. J. Zigler, K. V. Silvey, A. C. Bakke, W. W. Keeble, Y. Zhi, C. A. Reifsteck, M. Grompe, M. G. Brown, et al.
DNA Cross-Linker-Induced G2/M Arrest in Group C Fanconi Anemia Lymphoblasts Reflects Normal Checkpoint Function
Blood,
January 1, 1998;
91(1):
275 - 287.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. D'Andrea and M. Grompe
Molecular Biology of Fanconi Anemia: Implications for Diagnosis and Therapy
Blood,
September 1, 1997;
90(5):
1725 - 1736.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Qiao, A. Moss, and G. M. Kupfer
Fanconi Anemia Proteins Localize to Chromatin and the Nuclear Matrix in a DNA Damage- and Cell Cycle-regulated Manner
J. Biol. Chem.,
June 22, 2001;
276(26):
23391 - 23396.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
