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Rac controls nuclear entry

STAT5A stays out of the nucleus (blue) when Rac1 is removed (bottom).

Rac proteins are most familiar in the context of cytoskeletal regulation. Now, Kawashima et al. (page 937) find that Rac1 and its regulator help STAT transcriptional activators to get into the nucleus.

STAT proteins signal downstream of cytokine receptors. These researchers previously reported an association between STAT3 and the GTPase-activating protein MgcRacGAP. Here they report that Rac1 and MgcRacGAP bind STAT5A, and that the association between MgcRacGAP and STAT5A is enhanced by IL-3 signaling. Both Rac1 and MgcRacGAP were necessary for efficient entry of STAT5A into the nucleus, and in semipermeabilized cells a dominant-negative Rac1 prevented binding of STAT5A to importin-, and thus nuclear entry.

Others have previously shown, using armadillo proteins as import substrates, that Rac1 has a nuclear localization sequence (NLS) that is active when Rac1 is in its active, GTP-bound form. Unpublished data suggest, however, that it is an MgcRacGAP NLS that is required for STAT5A import.

MgcRacGAP is also found at the midbody, where it is phosphorylated to convert it into a Rho-GAP that helps complete cytokinesis. At the nuclear envelope it may undergo a different modification or activation, leading to release of STAT5A after nuclear import, as the group detected this dissociation event. The larger remaining question is whether cytoskeletal changes, such as those occurring when cells reach confluence, change Rac's regulation of nuclear entry and thus proliferation.

William A. Wells

wellsw{at}rockefeller.edu

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Related Article

Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors

Toshiyuki Kawashima, Ying Chun Bao, Yasushi Nomura, Yuseok Moon, Yukio Tonozuka, Yukinori Minoshima, Tomonori Hatori, Akiho Tsuchiya, Mari Kiyono, Tetsuya Nosaka, Hideaki Nakajima, David A. Williams, and Toshio Kitamura
J. Cell Biol. 2006 175: 937-946. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 820K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Related Collections Related Article Social Bookmarking                            What's this?