Table 1.

Functional Interaction Between AES/GRG5 and TF/Non-TF Proteins^a

AES/GRG5	TF/non-TF	Interaction domain of TF/non-TF	Interaction domain of AES/GRG5	Functional effect	Assay	Developmental/physiological effect	Refs
AES	Androgen receptor (AR)	N-terminus (aa. 1-559)	Q domain (aa. 1-129)	↓AR activity	Y2H, PD,CoIP RA, CFA	n/a	(Yu et al., 2001; Zhang et al., 2010)
AES	Bit1(non-TF)	n/a	n/a	↑Cytosolic Bit1-mediated apoptosis	Y2H, CoIP, CFA	Apoptosis	(Jan et al., 2004)
GRG5	mSix3, dSo (PD only), mSix6 (PD only)	eh-1 like motif in Six3 domain (aa. 1-183) conserved Phe-88 important	Q domain (1-134)	↑ mSix3 transcriptional repression	Y2H, PD, RA, ICC, no interaction via CoIP, AFA	Eye development	(Zhu et al., 2002)
GRG5	mSix2	No interaction	No interaction	n/a	PD	n/a	(Zhu et al., 2002)
AES*	Six3, Six6	Six domain for Six3 (∼ 1-205) and Six6 (1-127)	Q domain	↓ TLE-mediated Six3/6 transcriptional repression	Y2H, PD, ISH (me -AES and - Six3/6), AFA	Eye development	(Lopez-Rios et al., 2003)
AES	mSix2, dOptix	n/a	n/a	n/a	Y2H	n/a	(Lopez-Rios et al., 2003)
AES	Six1	n/a	n/a	n/a	Y2H, PD	n/a	(Lopez-Rios et al., 2003)
AES	mSix4	No interaction	No interaction	n/a	Y2H	n/a	(Lopez-Rios et al., 2003)
AES	PRDI-BF1	aa. 331-398	Q domain	Full length AES does not affect but truncated AES (ΔGP) inhibits PRDI-BF1- mediated activity	Y2H, PD, RA	n/a	(Ren et al., 1999)
AES	p65 subunit of NF-κB	Vicinity of p65 transactivation domain (aa. 477-521)	n/a	↓NF-κB-mediated activity	Y2H, PD, CoIP, RA	n/a	(Tetsuka et al., 2000)
GRG5*	mOct1	POU domain	Q domain	Potentially ↑ mOct1 activity	Y2H, PD, RA,	Potential↑ transcription of Gonadotropin releasing hormone	(Rave-Harel et al., 2005)
GRG5*	mMsx1	n/a	Q domain	↓ GRG1-mediated mMsx1 transcriptional repression	Y2H, PD, RA,	Potential↑ transcription of Gonadotropin releasing hormone	(Rave-Harel et al., 2005)
GRG5*, xAES*	Tcf1, dTCF, xTCF3	n/a	Q domain (aa. 1-106)	xAES and GRG5 ↑xTcf3 activity	Y2H, PD, ICC, RA, and/or AFA	xAES ↑xTcf3- mediated Xenopus axis duplication	(Roose et al., 1998; Brantjes et al., 2001)
GRG5, xAES	Lef1, mTcf3, mTcf4	No interaction	No interaction	n/a	Y2H	n/a	(Roose et al., 1998)
AES#	Lef1	n/a	n/a	↓ Lef1 activity	RA	n/a	(Arce et al., 2009)
AES*#	Lef1	n/a	n/a	↑ Lef1 activity	RA	n/a	(Beagle and Johnson, 2010)
GRG5*	mRunx2	Last 141 aa: VWRPY motif dispensable	Q and GP domain	↑ Runx2 activity	Y2H, CoIP, RA, AFA	Skeletal and growth development	(Wang et al., 2004)
AES*	PRH	No interaction	No interaction	↓ TLE1-mediated PRH transcriptional repression	CoIP, RA	n/a	(Swingler et al., 2004)
GRG5*	mNkx2.2, mNkx6.1	n/a	n/a	↓ GRG4-mediated mNkx -2.2 and -6.1 transcriptional repression	RA, AFA, ISH	Endogenous GRG5 not expressed during mNkx- mediated neuronal patterning	(Muhr et al., 2001)
GRG5	Hes1	No interaction	No interaction	Does not affect TLE- mediated Hes1 transcriptional repression	PD, CoIP, RA	n/a	(McLarren et al., 2001)
AES	LRP6-ICD (Non-TF)	n/a	n/a	LRP6-ICD ↓ AES-mediated LEF-1 activity	Y2H, CoIP, RA	n/a	(Beagle and Johnson, 2010)
AES*	HDRP (Non-TF)	aa. 178-343	First 17 aa dispensable	HDRP ↓ AES-mediated apoptosis	Y2H, PD, CoIP, CFA, RA	Apoptosis	(Zhang et al., 2008)
GRG5#	Pax5	n/a	n/a	Does not affect TLE- mediated Pax5 transcriptional repression		n/a	(Eberhard et al., 2000)
AES*#	rHNF3β	n/a	n/a	↑ HNF3β activity	RA	n/a	(Wang et al., 2000)
AES	TFIIE	n/a	n/a	Does not affect basal transcription of recombinant template	PD	n/a	(Yu et al., 2001)
AES	HDAC -1,-3	No interaction	No interaction		Y2H (HDAC1) PD (HDAC -1,-3)		(Yu et al., 2001; Zhang et al., 2008)
GRG5	HDAC1	No interaction	No interaction		CoIP		(Brantjes et al., 2001)

^aY2H, yeast-two-hybrid; RA, transcriptional reporter assay; PD, pull down; CoIP, co-immunoprecipitation assay; ISH, in situ hybridization; ICC, immunocytochemistry; AFA, functional assay in animal; CFA, cell culture based functional assay; TF/non-TF, Transcription Factor or non-Transcription Factor protein. Unless noted, the identified proteins are TFs. All TF/non-TF proteins are human unless noted and/or not identified by the study. d, Drosophila, me, medaka, x, Xenopus, r, rat, m, mouse.

^*represent opposing effects between long TLE/GRGs and AES/GRG5 for the identified TF/non-TF protein.

^#represent possible functional interactions for which interaction assays were not performed. n/a, information not reported or not identified/assayed.