title: TD-60 is required for interphase cell cycle progression.
abstract: We previously identified TD-60 (RCC2) as a mitotic centromere-associated protein that is necessary for proper completion of mitosis. We now report that TD-60 is an essential regulator of cell cycle progression during interphase. siRNA suppression blocks progression of mammalian G₁/S phase cells and progression of G₂ cells into mitosis. Prolonged arrest occurs both in non-transformed cells and in transformed cells lacking functional p53. TD-60 associates with Rac1 and Arf6 and has recently been demonstrated to be an element of α5β1 integrin and cortactin interactomes. These associations with known elements of cell cycle control, together with our data, suggest that TD-60 is an essential component of one or more signaling pathways that drive cell cycle progression. During mitosis, TD-60 is required for correct assembly of the mitotic spindle and activation of key mitotic proteins. In contrast, in interphase TD-60 promotes cell cycle progression through what must be distinct mechanisms. TD-60 thus appears to be one of the growing categories of proteins that "moonlight," or have more than one distinct cellular function.
authors: Tumor Development Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors: Mythili
authors: M
authors: Yenjerla
authors: Andreas
authors: A
authors: Panopoulos
authors: Caroline
authors: C
authors: Reynaud
authors: Rati
authors: R
authors: Fotedar
authors: Robert L
authors: RL
authors: Margolis
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D008938:Mitosis; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D020662:Guanine Nucleotide Exchange Factors; C477650:RCC2 protein, human; D034741:RNA, Small Interfering
keywords: G1 phase; G2 phase; RCC2; checkpoint; microtubules
references: Mol Cancer Ther. 2004 Sep;3(9):1079-90
references: 15367702
references: Science. 2001 May 25;292(5521):1540-3
references: 11375490
references: Mol Biol Cell. 1995 Jun;6(6):725-40
references: 7579691
references: J Biol Chem. 2012 Jul 13;287(29):24103-12
references: 22511753
references: BMC Cell Biol. 2011 Nov 13;12:49
references: 22078467
references: Dev Cell. 2003 Aug;5(2):295-307
references: 12919680
references: EMBO J. 1991 Jun;10(6):1555-64
references: 1851087
references: J Biol Chem. 1994 Oct 7;269(40):24542-5
references: 7929123
references: Nature. 1999 Jul 8;400(6740):178-81
references: 10408446
references: J Cell Biol. 2007 Nov 19;179(4):671-85
references: 18025303
references: Annu Rev Cell Dev Biol. 1997;13:261-91
references: 9442875
references: Genes Dev. 2001 Sep 1;15(17):2177-96
references: 11544175
references: Trends Cell Biol. 2001 Dec;11(12):497-503
references: 11719056
references: Science. 2008 Jan 25;319(5862):469-72
references: 18218899
references: Trends Cell Biol. 2001 Feb;11(2):49-54
references: 11166196
references: Genes Dev. 2004 Mar 1;18(5):512-27
references: 15014043
references: Cell. 2000 Jan 7;100(1):71-8
references: 10647932
references: J Proteomics. 2012 Jul 16;75(13):4184-5
references: 22579753
references: Sci STKE. 2005 Jan 11;2005(266):pl1
references: 15644491
references: Sci Signal. 2009 Sep 08;2(87):ra51
references: 19738201
references: J Cell Sci. 2001 Jul;114(Pt 14):2553-60
references: 11683383
references: Curr Opin Struct Biol. 2004 Dec;14(6):663-8
references: 15582389
references: J Cell Sci. 1991 Jul;99 ( Pt 3):523-34
references: 1939370
references: J Proteomics. 2012 Apr 3;75(7):2153-9
references: 22282019
references: Mol Cell Biol. 1992 Aug;12(8):3337-45
references: 1630449
references: Chromosoma. 1998 Dec;107(6-7):461-70
references: 9914378