2011
DOI: 10.1007/s13238-011-1015-4
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Microtubule-associated deacetylase HDAC6 promotes angiogenesis by regulating cell migration in an EB1-dependent manner

Abstract: Angiogenesis, a process by which the preexisting blood vasculature gives rise to new capillary vessels, is associated with a variety of physiologic and pathologic conditions. However, the molecular mechanism underlying this important process remains poorly understood. Here we show that histone deacetylase 6 (HDAC6), a microtubule-associated enzyme critical for cell motility, contributes to angiogenesis by regulating the polarization and migration of vascular endothelial cells. Inhibition of HDAC6 activity impa… Show more

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Cited by 72 publications
(56 citation statements)
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“…To begin to determine the molecular basis of this process, we focused on one of the most highly down-regulated genes identified in the microarray study, namely HDAC6, a cytoplasmic enzyme constitutively expressed in ECs which acetylates ␣-tubulin and cortactin, regulating cell motility and angiogenesis. [5][6][7] HDAC6 mRNA and protein levels were significantly decreased in Erg-deficient HUVECs, and this correlated with a significant increase in tubulin acetylation compared with control cells (Figure 5A-B). Similar regulation of HDAC6 levels and tubulin acetylation was observed after Erg inhibition in primary human dermal microvascular ECs (HMVECs; supplemental Figure 5).…”
Section: Erg Drives Expression Of Histone Deacetylase Hdac6mentioning
confidence: 89%
See 1 more Smart Citation
“…To begin to determine the molecular basis of this process, we focused on one of the most highly down-regulated genes identified in the microarray study, namely HDAC6, a cytoplasmic enzyme constitutively expressed in ECs which acetylates ␣-tubulin and cortactin, regulating cell motility and angiogenesis. [5][6][7] HDAC6 mRNA and protein levels were significantly decreased in Erg-deficient HUVECs, and this correlated with a significant increase in tubulin acetylation compared with control cells (Figure 5A-B). Similar regulation of HDAC6 levels and tubulin acetylation was observed after Erg inhibition in primary human dermal microvascular ECs (HMVECs; supplemental Figure 5).…”
Section: Erg Drives Expression Of Histone Deacetylase Hdac6mentioning
confidence: 89%
“…3 The class II histone deacetylase 6 (HDAC6), a known regulator of cell motility, 4 has been recently shown to be involved in EC migration and to support angiogenesis. 5 HDAC6 is expressed in many cells (including ECs) and localizes predominantly to the cytoplasm, binding to microtubules and deacetylating several cytosolic proteins, including ␣-tubulin 4,6 and cortactin. 7 Acetylation of tubulin, characteristic of stabilized microtubules, is thought to contribute to regulating microtubule dynamics, 8 while acetylation of cortactin is thought to modulate actin dynamics by regulating the interaction of cortactin with F-actin.…”
Section: Introductionmentioning
confidence: 99%
“…Horseradish peroxidase-conjugated secondary antibodies were from Amersham Biosciences. GFP-HDAC6, HA-HDAC6, and GFP-CLIP-170 expression plasmids and various truncated forms were constructed by PCR using pEG-FPN1 and pCMV-HA vectors as described previously (Zhou et al, 2009;Li et al, 2011;Sun et al, 2012Sun et al, , 2013a. HDAC6 and luciferase control siRNAs were synthesized by Invitrogen.…”
Section: Methodsmentioning
confidence: 99%
“…HDAC6 has been shown to participate in a wide range of cellular processes primarily through its deacetylation of α-tubulin, the actin-binding protein cortactin, and the molecular chaperone heat shock protein 90 (Hubbert et al, 2002;Matsuyama et al, 2002;Zhang et al, 2003;Kovacs et al, 2005;Zhang et al, 2007). In addition, HDAC6 can form various complexes with partner proteins to regulate physiological or pathological processes (Parmigiani et al, 2008;Huo et al, 2011;Li et al, 2011). Over the past decade, there has been tremendous effort to develop effective and specific HDAC6 inhibitors for the treatment of human diseases including cancer, although their mechanisms of action remain largely elusive (Aldana-Masangkay and Sakamoto, 2011;Dallavalle et al, 2012).…”
Section: Introductionmentioning
confidence: 99%
“…There is a limited research into the role of class IIb HDAC in angiogenesis, but nevertheless HDAC6 can be classiied as a pro-angiogenic factor as it induces cell migration by the deacetylation of cytoskeletal proteins [44,45]. Class III HDAC SIRT1 is also highly expressed in the vasculature during blood vessel growth where it controls the angiogenic activity of ECs.…”
Section: The Role Of Hdacs In Angiogenesis: Hdac-regulated Ecs Functimentioning
confidence: 99%