The Coactivator of Transcription CREB-binding Protein Interacts Preferentially with the Glycosylated Form of Stat5

Gewinner, Christina; Hart, Gerald W.; Zachara, Natasha E.; Cole, Robert N.; Beisenherz-Huss, Christian; Groner, Bernd

doi:10.1074/jbc.m306449200

Cited by 150 publications

(112 citation statements)

References 79 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…In addition to the crucial phosphorylation at Y694, glycosylation of Stat5a by O-linked N-acetyglucosamine (O-Glc-NAc) was detected in the nucleus of HC-11 mammary epithelial cells following Stat5 activation (Gewinner et al, 2004). Similar observations were made with Stat1, Stat3, and Stat6.…”

Section: Stat5 Activity Is Strictly Regulatedsupporting

confidence: 62%

Stat5 in the mammary gland: Controlling normal development and cancer

Barash

2006

Journal Cellular Physiology

View full text Add to dashboard Cite

The signal transducer and activator of transcription (Stat5) funnels extracellular signals of cytokines, hormones, and growth factors into transcriptional activity in the mammary gland. Postnatal development and functionality of this tissue is synchronized with the reproductive cycle. Consequently, Stat5 involvement in lobuloalveolar development, milk-protein synthesis, or tissue remodeling is dictated by the particular reproductive stage. Latent deregulation of Stat5 activity during the reproductive cycle predisposes the tissue to tumorigenesis at a later stage, when the female is no longer fertile. Accumulating data from studies with mouse models and breast-cancer specimens demonstrate a dual role for Stat5 in this context. It causes tumorigenesis, but delays metastasis progression. Consequently, Stat5 activity in breast-cancer specimens marks a better prognosis for survival.

show abstract

Section: Stat5 Activity Is Strictly Regulatedsupporting

confidence: 62%

Stat5 in the mammary gland: Controlling normal development and cancer

Barash

2006

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…The approach reported herein involves a nondestructive technique that does not require the removal of other PTMs to study O-GlcNAc. As such, the strategy should permit a direct examination of whether specific glycosylation and phosphorylation events are mutually exclusive in vivo, as suggested for the C-terminal domain of RNA polymerase II (29), or whether the two modifications coexist, as recently reported for the transcription factor signal transducer and activator of transcription 5 (Stat5) (30). Thus, the strategy is complementary to top-down MS approaches that can be used to simultaneously interrogate multiple PTMs from intact proteins (31).…”

Section: Discussionmentioning

confidence: 97%

Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain

Khidekel

Ficarro²,

Peters³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

280

250

View full text Add to dashboard Cite

“…Likewise, reduced binding of SP1 was associated with enhanced binding of the co-activator PCAF to the same area of the HAS2 promoter. O-GlcNAc modification of transcription factors such as SP1 and YY1 can also determine their capacity to bind a cofactor (39), another way to influence transcription. Altogether, the concomitant changes in the binding of transcriptional co-regulators at certain promoter sites further support the role of YY1 and SP1 in HAS2 transcription.…”

Section: Discussionmentioning

confidence: 99%

Cellular Content of UDP-N-acetylhexosamines Controls Hyaluronan Synthase 2 Expression and Correlates with O-Linked N-Acetylglucosamine Modification of Transcription Factors YY1 and SP1

Jokela

Makkonen

Oikari

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Hyaluronan, a high molecular mass polysaccharide on the vertebrate cell surface and extracellular matrix, is produced at the plasma membrane by hyaluronan synthases using UDP-GlcNAc and UDP-GlcUA as substrates. The availability of these UDP-sugar substrates can limit the synthesis rate of hyaluronan. In this study, we show that the cellular level of UDP-HexNAc also controls hyaluronan synthesis by modulating the expression of HAS2 (hyaluronan synthase 2). Hyaluronan, a non-sulfated glycosaminoglycan present on the vertebrate cell surface and extracellular matrix, is involved in cellular functions, including migration, proliferation, adhesion, and various signaling systems, by its unique physicochemical properties and interactions with specific cell surface receptors (1). Hyaluronan is synthesized by HAS1-3, integral plasma membrane proteins that use cytosolic UDP-GlcNAc and UDPGlcUA as substrates to produce the long linear hyaluronan chains. During its synthesis, the growing hyaluronan chain runs through a pore in the plasma membrane into the extracellular matrix (2).Changes in hyaluronan production have been associated mostly with the expression level of HAS genes (3-6), especially in keratinocytes (7-13). Of the three genes, particularly HAS2 is subject to regulation by growth factors, cytokines, and hormones (4,14,15). In keratinocyte cultures, EGF, keratinocyte growth factor, TNF␣, and retinoic acid induce, whereas TGF␤ inhibits, HAS2 expression (8, 10, 13, 16). Accordingly, the HAS2 promoter has been shown to contain functional response elements (REs) 3 for different transcription factors, including retinoid acid receptor, NF-B, CREB1 (cAMP response elementbinding protein 1), and SP1 (specificity protein 1) (7,11,16).Besides by the protein expression of hyaluronan synthase (HAS) enzymes, hyaluronan synthesis is also controlled by the availability of the hyaluronan precursors, the substrates of HAS. Raising cellular UDP-GlcUA content stimulates hyaluronan synthesis, whereas a low concentration of UDP-GlcUA can limit the synthesis (12, 17). We have shown that the same applies to UDP-GlcNAc: limiting or increasing its content stimulates and inhibits, respectively, the synthesis of hyaluronan (18).The cellular content of UDP-GlcNAc makes an interesting connection between hyaluronan synthesis and cellular energy metabolism. UDP-GlcNAc is a product of the hexosamine synthesis pathway, into which 2-5% of the cellular influx of glucose is shunted (19). The rate-limiting step in hexosamine synthesis from glucose to UDP-GlcNAc is considered to be the GFAT1 (glutamine:fructose-6-phosphate amidotransferase 1) and GFAT2 isoenzymes (20). The flux of glucose through the hexosamine pathway serves as a cellular sensor of glucose availability, and it regulates the expression of a number of genes 3 The abbreviations used are: RE, response element; HAS, hyaluronan synthase; CBP, cAMP response element-binding protein-binding protein; PCAF, p300/CBP-associated factor.

show abstract

The Coactivator of Transcription CREB-binding Protein Interacts Preferentially with the Glycosylated Form of Stat5

Cited by 150 publications

References 79 publications

Stat5 in the mammary gland: Controlling normal development and cancer

Stat5 in the mammary gland: Controlling normal development and cancer

Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain

Cellular Content of UDP-N-acetylhexosamines Controls Hyaluronan Synthase 2 Expression and Correlates with O-Linked N-Acetylglucosamine Modification of Transcription Factors YY1 and SP1

Contact Info

Product

Resources

About