High impact information on HSL1

• Enhancement of microtubule shrinkage at the bud neck required the Par-1-related, septin-dependent kinases (SDK) Hsl1 and Gin4 [1].
• We demonstrated previously that Hsl1p, a protein kinase that inhibits the Swe1p protein kinase in a bud morphogenesis checkpoint, is targeted for ubiquitin-mediated turnover by the anaphase-promoting complex (APC) [2].
• Finally, this bacterially expressed Hsl1p fusion protein interacted with Cdc20p and Cdh1p either translated in vitro or expressed in and purified from insect cells [2].
• Kcc4, like Hsl1 and Gin4, was found to localize to the bud neck in a septin-dependent fashion [3].
• In addition, we have isolated a dosage-dependent suppressor, OSS1, of hsl1 and hsl7 [4].

Biological context of HSL1

• The nim1-related protein kinase, Hsl1, induces entry into mitosis by negatively regulating Swe1 [3].
• Hsl7, in turn, presents its cargo of bound Swe1, allowing phosphorylation by Hsl1 [5].
• Hsl1 is a large (1,518-residue) protein kinase with an N-terminal catalytic domain and a very long C-terminal extension [5].
• Our results suggest that binding to multiple septins activates Hsl1 kinase activity, thereby promoting cell cycle progression [6].
• We first identified a regulatory region of Hsl1 that physically associates with the kinase domain and found that it performs an autoinhibitory function both in vivo and in vitro [6].

Anatomical context of HSL1

• We have studied the molecular mechanism by which assembly of the yeast septin cytoskeleton is monitored and coordinated with cell cycle progression by analyzing a key regulatory protein kinase, Hsl1, that becomes activated only when the septin cytoskeleton is properly assembled [6].

Physical interactions of HSL1

• Also consistent with the two-hybrid results, Hsl7 coimmunoprecipitates with full-length Hsl1 less efficiently than with a C-terminal fragment of Hsl1 [5].
• In medium with a high concentration of Ca2+, Hsl1 was delocalized from the bud neck and destabilized in a manner dependent on both calcineurin and Mck1 [7].
• The cell cycle regulator Nik1 (Hsl1) is a protein kinase that interacts with the Cdc28 complex [8].

Regulatory relationships of HSL1

• Swe1 is itself negatively regulated by Hsl1, a Nim1-related protein kinase, and by Hsl7, a presumptive protein-arginine methyltransferase [9].
• Hsl1p accumulates periodically during the cell cycle and promotes the periodic phosphorylation of Hsl7p [10].
• Although inactivation of Hsl1 is sufficient to suppress the defect in filamentous growth caused by inactivation of Tec1 or Flo8, it is insufficient to promote filamentous growth in the absence of both factors [11].

Other interactions of HSL1

• Interestingly, hsl1 kcc4 gin4 triple mutants develop a cellular morphology extremely similar to that of septin mutants [3].
• In contrast, mutations affecting the other two Nim1p-related kinases in S. cerevisiae, Hsl1p and Kcc4p, produce no detectable effect on septin organization [12].
• Localization of Hsl1p to the neck requires Elm1p function [13].
• In acm1Delta strains, Cdh1 localization to the bud neck and association with two substrates, Clb2 and Hsl1, were strongly enhanced [14].
• In coimmunoprecipitation studies, the D box of full-length Hsl1p was critical for association with Cdc20p, whereas the KEN box was important for association with Cdh1p [2].

Analytical, diagnostic and therapeutic context of HSL1

• With the use of both the two-hybrid method and in vitro binding assays, we found that Hsl7 contains distinct binding sites for Hsl1 and Swe1 [9].

References